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Intervention Protocol

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Belatacept for kidney transplant recipients

  1. Philip Masson1,*,
  2. Lorna Henderson2,
  3. Jeremy R Chapman3,
  4. Jonathan C Craig1,4,
  5. Angela C Webster1,4,5

Editorial Group: Cochrane Renal Group

Published Online: 15 AUG 2013

DOI: 10.1002/14651858.CD010699


How to Cite

Masson P, Henderson L, Chapman JR, Craig JC, Webster AC. Belatacept for kidney transplant recipients (Protocol). Cochrane Database of Systematic Reviews 2013, Issue 8. Art. No.: CD010699. DOI: 10.1002/14651858.CD010699.

Author Information

  1. 1

    The University of Sydney, Sydney School of Public Health, Sydney, Australia

  2. 2

    Royal Infirmary of Edinburgh, Department of Renal Medicine, Edinburgh, UK

  3. 3

    Westmead Millennium Institute, The University of Sydney at Westmead, Centre for Transplant and Renal Research, Westmead, NSW, Australia

  4. 4

    The Children's Hospital at Westmead, Cochrane Renal Group, Centre for Kidney Research, Westmead, NSW, Australia

  5. 5

    The University of Sydney at Westmead, Centre for Transplant and Renal Research, Westmead Millennium Institute, Westmead, NSW, Australia

*Philip Masson, Sydney School of Public Health, The University of Sydney, Sydney, Australia. philip_masson@hotmail.com.

Publication History

  1. Publication Status: New
  2. Published Online: 15 AUG 2013

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This is not the most recent version of the article. View current version (24 NOV 2014)

 

Background

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
 

Description of the condition

Kidney transplantation offers suitable recipients with end-stage kidney disease (ESKD) potential for improved quality and length of life compared with remaining on chronic dialysis (Wolfe 1999). Mismatch of organ demand and availability has prompted the use of strategies both to expand the donor pool and prolong kidney transplant survival. 

Short-term kidney transplant survival has improved significantly over the last 20 years since the introduction of calcineurin inhibitors (CNI). However, improvements in medium- to long-term recipient and kidney transplant survival have not been commensurate with this outcome owing to these same agents' immunologically, and non-immunologically-mediated side-effects. Although one-year kidney transplant survival in the USA is 95% and 89% respectively for recipients of living and deceased donor kidneys, five-year kidney transplant survival falls to 80% and 67% respectively (OPTN 2010). This trend is also evident in Australia and New Zealand, where one-year first kidney transplant survival for living and deceased donor kidneys is 97% and 92% respectively, falling to 90% and 82% by five years (ANZDATA 2011).

Death with a functioning kidney transplant and interstitial fibrosis/tubular atrophy (IF/TA) are the biggest causes of kidney transplant loss and failure respectively. Cardiovascular disease and cancer are the biggest causes of death among kidney transplant recipients. Cardiovascular morbidity and mortality may be influenced directly by CNI side effects which include nephrotoxicity, hypertension, diabetes and hyperlipidaemia (Meier-Kriesche 2004; Nankivell 2003; Vanrenterghem 2008; Vincenti 2007). IF/TA is also associated with CNI use (Nankivell 2004). Although prolonged dose-related afferent and efferent arteriolar vasoconstriction may cause ischaemic structural changes in the kidney, dose minimisation strategies and non-adherence may result in ineffective control of donor-specific antibody production and consequent chronic antibody-mediated rejection. Conversely, over-immunosuppression, and polyoma (BK) virus-related nephropathy may be further contributory factors in chronic kidney transplant attrition.

Cardiovascular morbidity and mortality associated with CNI-based immunosuppression regimens, and avoidance of long-term kidney transplant loss from IF/TA therefore present the biggest challenges to improving medium- and long-term recipient and kidney transplant outcomes. 

 

Description of the intervention

Belatacept – a biologic immunosuppressive agent – is an inhibitor of T-cell co-stimulation, which was approved by the US Food and Drug Administration (FDA) in June 2011 for use in adult kidney transplant recipients. The FDA considered results from three randomised-controlled trials (RCT) that involved 1425 recipients which compared belatacept and cyclosporin in a regimen with concomitant use of mycophenolate mofetil (MMF) and steroids in its approval process. In all three studies, belatacept was demonstrated to be non-inferior to cyclosporin in preventing acute rejection in kidney transplant recipients (BENEFIT 2010; BENEFIT-EXT 2010; Vincenti 2007).

 

How the intervention might work

Belatacept is a direct antagonist of the ligands CD80 and CD86 present on antigen-presenting cells which prevents T-cell CD28 receptor activation. This is designed to eliminate the non-immunological activity associated with conventional immunosuppressive agents while providing potent inhibition of T-cell activation and proliferation required to prevent acute rejection (Sayegh 1998). Clinically, belatacept offers the potential for effective maintenance immunosuppression and improved long-term kidney transplant and recipient survival by minimising the cardiovascular burden associated with CNIs and steroids.

 

Why it is important to do this review

The current key barriers to long-term kidney transplant survival are death with a functioning graft and interstitial IF/TA (UK Renal Registry 2010). Adverse effects of induction and maintenance immunosuppression are significant risk factors for death and kidney transplant attrition, and therefore also present the greatest opportunity for improving long-term outcomes in kidney transplantation.

Following a kidney transplant, immunologically-mediated organ damage is prevented using immunosuppressive protocols typically consisting of an intensive induction period followed by a less intensive maintenance phase. Induction agents include: anti-T cell antibodies (e.g. polyclonal anti-thymocyte globulin (ATG)); interleukin-2 receptor (anti-CD25) antibodies (e.g. basiliximab or daclizumab); anti-CD52 antibodies (e.g. alemtuzumab); anti-B cell antibodies (e.g. rituximab), and high-dose steroids (methylprednisolone). Maintenance phase immunosuppression generally combines three main groups of drugs, each directed to a different cell-signalling messenger involved in T-cell activation, namely: anti-proliferatives (e.g. azathioprine, MMF); CNIs (e.g. cyclosporin, tacrolimus), and steroids (prednisolone). The integrated use of these induction and maintenance agents varies geographically, and between recipient groups based on a combination of the availability of healthcare resources, clinician perception of agents’ relative potencies and side-effects, as well as estimates of recipient immunological, malignant and metabolic risk (Webster 2009).

Several strategies exist to avoid the side-effects associated with CNIs. CNI avoidance (ELITE SYMPHONY 2007), minimisation (ORION 2011) and substitution (CONVERT 2009) strategies have been attempted with mixed results, the optimal balance between sufficient immunosuppression to avoid kidney transplant damage and excessive immunosuppression causing nephrotoxicity remaining elusive. Belatacept is a first-in-class co-stimulation blocker, proposed as an alternative maintenance immunosuppressant able to combine equivalent prophylaxis against acute rejection with favourable effects on long-term kidney transplant outcomes, and cardiovascular morbidity and mortality (BENEFIT 2010; BENEFIT-EXT 2010; Vincenti 2007).

However, the widespread clinical use of belatacept requires a full evaluation of its benefits in the context of any associated harms. Post-transplant lymphoproliferative disorder is the most serious adverse event reported to be associated with belatacept's use (Vincenti 2005), predominantly affecting Epstein-Barr virus negative kidney transplant recipients. Licensing of belatacept has been restricted to the less-intense dosing on the basis of a stronger association between belatacept and post-transplant lymphoproliferative disorder with the more-intense dosing schedule, but further clarification of the nature, confounders, and effect modifiers of this association are urgently required by the transplant community.

 

Objectives

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest

The objectives of this review are to:

  1. Compare the relative efficacy of belatacept versus any other immunosuppressive co-intervention for preventing acute rejection and maintaining kidney transplant function, and composite kidney transplant and recipient survival.
  2. Compare the incidence of several adverse events: Post-transplant lymphoproliferative disorder; other malignancies; IF/TA; infective complications; deterioration in blood pressure, lipid and glycaemic control.
  3. Assess any variation in effects by study, intervention and recipient characteristics, including: differences in pre-transplant Epstein-Barr virus status; belatacept dosing regimen; and donor-category (living, standard criteria deceased, or extended criteria deceased).

 

Methods

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
 

Criteria for considering studies for this review

 

Types of studies

All RCTs and quasi-RCTs (in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) where belatacept was used in a primary immunosuppression regimen to treat kidney transplant recipients.

 

Types of participants

 

Inclusion criteria

Adults and children receiving a kidney transplant from a living or deceased donor (standard or extended criteria), in whom belatacept was tested versus any other immunosuppressive agent in a primary induction and maintenance regimen.

 

Exclusion criteria

Kidney transplant recipients in whom belatacept was tested against any other immunosuppressive agent in a secondary immunosuppression regimen, that is, when treatment was changed due to acute or chronic rejection, IF/TA or CNI toxicity. Recipients who received another solid organ in addition to a kidney transplant (e.g. kidney and pancreas, kidney and liver).

 

Types of interventions

  1. Belatacept given in combination with any other immunosuppressive co-intervention in which control recipients receive no belatacept, placebo, or another agent that the belatacept arm did not receive
  2. Belatacept given in combination with any other immunosuppressive co-intervention in which control recipients receive a dose comparison (e.g. high dose versus low dose belatacept).

 

Types of outcome measures

  1. Mortality: death with a functioning kidney transplant
  2. Loss of kidney transplant censored for death
  3. Loss of kidney transplant, or death with a functioning kidney transplant
  4. Kidney transplant function measures: measured glomerular filtration rate (GFR), estimated GFR (eGFR)
  5. Incidence of acute rejection
  6. Incidence and grade of IF/TA
  7. Incidence of delayed kidney transplant function (DGF)
  8. Cardiovascular measures: mean, or change in systolic and diastolic blood pressure (SBP, DBP), total cholesterol, high density lipoprotein (HDL), non-HDL, low density lipoprotein (LDL), triglycerides (TG), serum blood glucose,
  9. Incidence of infections: cytomegalovirus (CMV, syndrome and disease), polyoma virus (BK viraemia and BK virus-associated nephropathy), pneumonia, tuberculosis (TB), urinary tract infection (UTI)
  10. Incidence of malignancies: all-cause, basal cell carcinoma (BCC), squamous cell carcinoma (SCC), post-transplant lymphoproliferative disorder (PTLD)
  11. Incidence of other adverse events

 

Primary outcomes

  1. Recipient mortality (all-cause)
  2. Loss of a kidney transplant censored for death with a functioning transplant (i.e. loss of transplant function resulting in dialysis-dependence)
  3. Recipient and kidney transplant survival.

 

Secondary outcomes

  1. Measured GFR (iothalamate clearance)
  2. Calculated GFR (modification of diet in renal disease (MDRD))
  3. Incidence and grade of acute rejection (biopsy-proven)
  4. Incidence and grade of IF/TA (biopsy-proven)
  5. Incidence of DGF: dialysis treatment required in the first week after transplantation
  6. Incidence of malignancy: any, BCC, SCC, PTLD diagnosed by clinical/radiological appearance, histology or as specified
  7. Incidence and severity of infection: CMV, BK virus, TB, UTI, pneumonia (diagnosed by clinical/radiological/microbiological culture, antibody or antigen testing or as specified)
  8. Incidence of new-onset diabetes after transplantation
  9. Incidence of hypertension (absolute SBP/DBP 140/90 mm Hg; use of 1 to 2 or 3 or more antihypertensive drugs)
  10. Incidence of dyslipidaemia (serum total cholesterol, HDL, non-HDL, LDL, TG)
  11. Incidence of other adverse events: diarrhoea, lymphocoele.

 

Search methods for identification of studies

 

Electronic searches

We will search the Cochrane Renal Group's Specialised Register through contact with the Trials' Search Co-ordinator using search terms relevant to this review.

The Cochrane Renal Group’s Specialised Register contains studies identified from:

  1. Quarterly searches of the Cochrane Central Register of Controlled Trials (CENTRAL)
  2. Weekly searches of MEDLINE OVID SP
  3. Handsearching of renal-related journals and the proceedings of major renal conferences
  4. Searching of the current year of EMBASE OVID SP
  5. Weekly current awareness alerts for selected renal journals
  6. Searches of the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.

Studies contained in the Specialised Register are identified through search strategies for CENTRAL, MEDLINE, and EMBASE based on the scope of the Cochrane Renal Group. Details of these strategies, as well as a list of handsearched journals, conference proceedings and current awareness alerts, are available in the Specialised Register section of information about the Cochrane Renal Group.

See Appendix 1 for search terms used in strategies for this review.

 

Searching other resources

  1. Reference lists of clinical practice guidelines, review articles and relevant studies.
  2. Letters seeking information about unpublished or incomplete trials to investigators known to be involved in previous studies.

 

Data collection and analysis

 

Selection of studies

The search strategy described will be used to obtain titles and abstracts of studies that may be relevant to the review. The titles and abstracts will be screened independently by two authors, who will discard studies that are not applicable; however studies and reviews that might include relevant data or information on trials will be retained initially. Two authors will independently assess retrieved abstracts and, if necessary the full text, of these studies to determine which studies satisfy the inclusion criteria.

 

Data extraction and management

Data extraction will be carried out independently by two authors using standard data extraction forms. Studies reported in non-English language journals will be translated before assessment. Where more than one publication of one study exists, reports will be grouped together and only the publication with the most complete data will be used in the analyses. Where relevant outcomes are only published in earlier versions this data will be used. Any discrepancy between published versions will be highlighted.

 

Assessment of risk of bias in included studies

The following items will be independently assessed by two authors using the risk of bias assessment tool (Higgins 2011) (see Appendix 2).

  • Was there adequate sequence generation (selection bias)?
  • Was allocation adequately concealed (selection bias)?
  • Was knowledge of the allocated interventions adequately prevented during the study (detection bias)?
    • Participants and personnel
    • Outcome assessors
  • Were incomplete outcome data adequately addressed (attrition bias)?
  • Are reports of the study free of suggestion of selective outcome reporting (reporting bias)?
  • Was the study apparently free of other problems that could put it at a risk of bias?

 

Measures of treatment effect

For dichotomous outcomes (e.g. acute rejection or no acute rejection) results will be expressed as risk ratios (RR) with 95% confidence intervals (CI). Where continuous scales of measurement are used to assess the effects of treatment (e.g. measured or calculated GFR, blood pressure), the mean difference (MD) will be used, or the standardised mean difference (SMD) if different scales have been used.

Studies reporting change differences and end of treatment differences will be entered into the same analyses (e.g. end of treatment mean GFR and mean change in GFR from baseline). Missing standard deviations will be imputed using the average value from other studies in the same meta-analysis.

 

Dealing with missing data

Any further information required from the original author will be requested by written correspondence (e.g. emailing and/or writing to corresponding author/s) and any relevant information obtained in this manner will be included in the review. Evaluation of important numerical data such as screened, randomised patients as well as intention-to-treat (ITT), as-treated and per-protocol (PP) population will be carefully performed. Attrition rates, for example drop-outs, losses to follow-up and withdrawals will be investigated. Issues of missing data and imputation methods (for example, last-observation-carried-forward (LOCF)) will be critically appraised (Higgins 2011).

 

Assessment of heterogeneity

Heterogeneity will be analysed using a Chi² test on N-1 degrees of freedom, with an alpha of 0.05 used for statistical significance and with the I² test (Higgins 2003). I² values of 25%, 50% and 75% correspond to low, medium and high levels of heterogeneity.

 

Assessment of reporting biases

If possible, funnel plots will be used to assess for the potential existence of small study bias (Higgins 2011).

 

Data synthesis

Data will be pooled using the random-effects model but the fixed-effect model will also be used to ensure robustness of the model chosen and susceptibility to outliers.

 

Subgroup analysis and investigation of heterogeneity

Subgroup analysis will be used to explore possible sources of heterogeneity (e.g. pre-transplant EBV status, donor-criteria subtype). Heterogeneity among participants could be related to age, ethnicity, degree of sensitisation (percentage of panel reactive antibodies (PRA)), or underlying aetiology of ESKD. Heterogeneity in treatments could be related to the dose and duration of therapy (belatacept high versus low dose), induction agent used (anti-thymocyte globulin versus interleukin-2), or comparator CNI (cyclosporin versus tacrolimus). Adverse effects will be tabulated and assessed with descriptive techniques, as they are likely to be different for the various agents used. Where possible, the risk difference with 95% CI will be calculated for each adverse effect, either compared to no treatment or to another agent.

 

Sensitivity analysis

We will perform sensitivity analyses in order to explore the influence of the following factors on effect size:

  • repeating the analysis excluding unpublished studies
  • repeating the analysis taking account of risk of bias
  • repeating the analysis excluding any very long or large studies to establish how much they dominate the results
  • repeating the analysis excluding studies using the following filters: diagnostic criteria, language of publication, source of funding (industry versus other), and country.

 

Acknowledgements

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest

  • We are grateful to the Cochrane Renal Group for their assistance, in particular, Gail Higgins who developed the search strategy.
  • We would also like to thank the referees for their comments and feedback during the preparation of this protocol.

 

Appendices

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
 

Appendix 1. Electronic search strategies


DatabaseSearch terms

CENTRAL
  1. MeSH descriptor Kidney Transplantation, this term only
  2. (kidney transplant*):ti,ab,kw in Clinical Trials
  3. (#1 OR #2)
  4. (Belatacept):ti,ab,kw in Clinical Trials
  5. (lea29y):ti,ab,kw in Clinical Trials
  6. (bms 224818):ti,ab,kw in Clinical Trials
  7. (costimulation blocker*):ti,ab,kw or (co-stimulation blocker*):ti,ab,kw in Clinical Trials
  8. (#4 OR #5 OR #6 OR #7)
  9. (#3 AND #8)

MEDLINE (OVID SP)
  1. Kidney Transplantation/
  2. Belatacept.tw.
  3. lea29y.tw.
  4. "bms 224818".tw.
  5. (costimulation blocker$ or co-stimulation blocker$).tw.
  6. or/2-5
  7. and/1,6

EMBASE (OVID SP)
  1. exp kidney transplantation/
  2. belatacept/
  3. Belatacept.tw.
  4. lea 29y.tw.
  5. lea29y.tw.
  6. bms 224818.tw.
  7. (costimulation blocker$ or co-stimulation blocker$).tw.
  8. or/2-7
  9. and/1,8



 

Appendix 2. Risk of bias assessment tool


Potential source of biasAssessment criteria

Random sequence generation

Selection bias (biased allocation to interventions) due to inadequate generation of a randomised sequence
Low risk of bias: Random number table; computer random number generator; coin tossing; shuffling cards or envelopes; throwing dice; drawing of lots; minimization (minimization may be implemented without a random element, and this is considered to be equivalent to being random).

High risk of bias: Sequence generated by odd or even date of birth; date (or day) of admission; sequence generated by hospital or clinic record number; allocation by judgement of the clinician; by preference of the participant; based on the results of a laboratory test or a series of tests; by availability of the intervention.

Unclear: Insufficient information about the sequence generation process to permit judgement.

Allocation concealment

Selection bias (biased allocation to interventions) due to inadequate concealment of allocations prior to assignment
Low risk of bias: Randomisation method described that would not allow investigator/participant to know or influence intervention group before eligible participant entered in the study (e.g. central allocation, including telephone, web-based, and pharmacy-controlled, randomisation; sequentially numbered drug containers of identical appearance; sequentially numbered, opaque, sealed envelopes).

High risk of bias: Using an open random allocation schedule (e.g. a list of random numbers); assignment envelopes were used without appropriate safeguards (e.g. if envelopes were unsealed or non-opaque or not sequentially numbered); alternation or rotation; date of birth; case record number; any other explicitly unconcealed procedure.

Unclear: Randomisation stated but no information on method used is available.

Blinding of participants and personnel

Performance bias due to knowledge of the allocated interventions by participants and personnel during the study
Low risk of bias: No blinding or incomplete blinding, but the review authors judge that the outcome is not likely to be influenced by lack of blinding; blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.

High risk of bias: No blinding or incomplete blinding, and the outcome is likely to be influenced by lack of blinding; blinding of key study participants and personnel attempted, but likely that the blinding could have been broken, and the outcome is likely to be influenced by lack of blinding.

Unclear: Insufficient information to permit judgement

Blinding of outcome assessment

Detection bias due to knowledge of the allocated interventions by outcome assessors
Low risk of bias: No blinding of outcome assessment, but the review authors judge that the outcome measurement is not likely to be influenced by lack of blinding; blinding of outcome assessment ensured, and unlikely that the blinding could have been broken.

High risk of bias: No blinding of outcome assessment, and the outcome measurement is likely to be influenced by lack of blinding; blinding of outcome assessment, but likely that the blinding could have been broken, and the outcome measurement is likely to be influenced by lack of blinding.

Unclear: Insufficient information to permit judgement

Incomplete outcome data

Attrition bias due to amount, nature or handling of incomplete outcome data
Low risk of bias: No missing outcome data; reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing bias); missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size; missing data have been imputed using appropriate methods.

High risk of bias: Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce clinically relevant bias in intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes enough to induce clinically relevant bias in observed effect size; ‘as-treated’ analysis done with substantial departure of the intervention received from that assigned at randomisation; potentially inappropriate application of simple imputation.

Unclear: Insufficient information to permit judgement

Selective reporting

Reporting bias due to selective outcome reporting
Low risk of bias: The study protocol is available and all of the study’s pre-specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre-specified way; the study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified (convincing text of this nature may be uncommon).

High risk of bias: Not all of the study’s pre-specified primary outcomes have been reported; one or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. subscales) that were not pre-specified; one or more reported primary outcomes were not pre-specified (unless clear justification for their reporting is provided, such as an unexpected adverse effect); one or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta-analysis; the study report fails to include results for a key outcome that would be expected to have been reported for such a study.

Unclear: Insufficient information to permit judgement

Other bias

Bias due to problems not covered elsewhere in the table
Low risk of bias: The study appears to be free of other sources of bias.

High risk of bias: Had a potential source of bias related to the specific study design used; stopped early due to some data-dependent process (including a formal-stopping rule); had extreme baseline imbalance; has been claimed to have been fraudulent; had some other problem.

Unclear: Insufficient information to assess whether an important risk of bias exists; insufficient rationale or evidence that an identified problem will introduce bias.



 

Contributions of authors

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest

  1. Design of the study: PM, LH, JRC, JCC, AW
  2. Draft the protocol: PM; LH, JRC, JCC, AW
  3. Study selection: PM, LH
  4. Extract data from studies: PM, LH
  5. Enter data into RevMan: PM, LH
  6. Carry out the analysis: PM, AW
  7. Interpret the analysis: PM, AW, JCC
  8. Draft the final review: PM, LH, JRC, JCC, AW
  9. Disagreement resolution: AW, JCC
  10. Update the review: PM, LH, AW, JRC, JCC

 

Declarations of interest

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest

None known.

References

Additional references

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Acknowledgements
  7. Appendices
  8. Contributions of authors
  9. Declarations of interest
  10. Additional references
ANZDATA 2011
  • Clayton P, Campbell S, Hurst K, McDonald S, Chadban S. ANZDATA Registry Report 2011. Chapter 8: Transplantation; 25-31. http://www.anzdata.org.au/anzdata/AnzdataReport/34thReport/2011c08_transplantation_v1.7.pdf (accessed 17 July 2013).
BENEFIT 2010
BENEFIT-EXT 2010
CONVERT 2009
  • Schena FP, Pascoe MD, Alberu J, del Carmen Rial M, Oberbauer R, Brennan DC, et al. Conversion from calcineurin inhibitors to sirolimus maintenance therapy in renal allograft recipients: 24-month efficacy and safety results from the CONVERT trial. Transplantation 2009;87(2):233-42. [MEDLINE: 19155978]
ELITE SYMPHONY 2007
Higgins 2003
Higgins 2011
  • Higgins JP, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Meier-Kriesche 2004
Nankivell 2003
  • Nankivell B, Borrows R, Fung C, O'Connell P, Allen R, Chapman J. The natural history of chronic allograft nephropathy. New England Journal of Medicine 2003;349(24):2326-33. [MEDLINE: 14668458]
Nankivell 2004
OPTN 2010
  • Anonymous. Organ Procurement and Transplantation Network. http://optn.transplant.hrsa.gov/lData/ (accessed 17 July 2013).
ORION 2011
Sayegh 1998
  • Sayegh M, Turka L. The role of T-cell costimulatory activation pathways in transplant rejection. New England Journal of Medicine 1998;338(25):1813-21. [MEDLINE: 9632449]
UK Renal Registry 2010
  • The Renal Association. UK Renal Registry Thirteenth Annual Report, 2010. Available from http://www.renalreg.com/Reports/2010.html (accessed 17 July 2013).
Vanrenterghem 2008
Vincenti 2005
Vincenti 2007
Webster 2009
Wolfe 1999
  • Wolfe RA, Ashby VB, Milford EL, Ojo A, Ettenger R, Agodoa L, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. New England Journal of Medicine 1999;341(23):1725-30. [MEDLINE: 10580071]