Practical Recommendations for Long-term Management of Modifiable Risks in Kidney and Liver Transplant Recipients: A Guidance Report and Clinical Checklist by the Consensus on Managing Modifiable Risk in Transplantation (COMMIT) Group.

TLDR: In this article, the authors provide specific, practical recommendations, through the discussion of current evidence and best practice, for the management of modifiable risks in those kidney and liver transplant patients who have survived the first postoperative year.

Abstract: Short-term patient and graft outcomes continue to improve after kidney and liver transplantation, with 1-year survival rates over 80%; however, improving longer-term outcomes remains a challenge. Improving the function of grafts and health of recipients would not only enhance quality and length of life, but would also reduce the need for retransplantation, and thus increase the number of organs available for transplant. The clinical transplant community needs to identify and manage those patient modifiable factors, to decrease the risk of graft failure, and improve longer-term outcomes.COMMIT was formed in 2015 and is composed of 20 leading kidney and liver transplant specialists from 9 countries across Europe. The group's remit is to provide expert guidance for the long-term management of kidney and liver transplant patients, with the aim of improving outcomes by minimizing modifiable risks associated with poor graft and patient survival posttransplant.The objective of this supplement is to provide specific, practical recommendations, through the discussion of current evidence and best practice, for the management of modifiable risks in those kidney and liver transplant patients who have survived the first postoperative year. In addition, the provision of a checklist increases the clinical utility and accessibility of these recommendations, by offering a systematic and efficient way to implement screening and monitoring of modifiable risks in the clinical setting.

Figures

FIGURE 4. Causes of late allograft loss in liver transplant recipients. Diabetes, hypertension, hyperlipidemia, high variability and nonadherence to immunosuppressive agents are modifiable risk factors. Figure based on data from Hübscher 2011, Bekker 2009, O’Leary 2014, Supelana 2014, Charlton 2013 and Kamar 2008.26-31

TABLE 7. Highly modifiable risk factors for de novo DSAs20,270,273

TABLE 8. DSA assessment postkidney transplantation

FIGURE 9. Infections in solid organ transplant recipients. The timeline of infections after organ transplantation. The risk for infection after organ transplantation follows a standard pattern with routine immunosuppression and infectious exposures. The potential pathogens for which the risk is modified by prophylaxis, including vaccinations and antimicrobial agents, are indicated (*). Individual risk is modified by events such as surgery, treatment of graft rejection, or malignancy. Note that graft rejection and drug reactions may be among noninfectious causes of fever in transplant recipients. JC virus, John Cunningham virus; HSV, herpes simplex virus. Modified with permission from the author; reprinted with permission from Fishman JA. Opportunistic infections – coming to the limits of immunosuppression? Cold Spring Harb Perspect Med. 2013;3:1–14; original source of data: Fishman J. Infection in solid-organ transplant recipients.N Engl J Med. 2007;357:2601–2614. Adaptations are themselves works protected by copyright. So in order to publish this adaptation, authorization must be obtained both from the owner of the copyright in the original work and from the owner of copyright in the translation or adaptation.195,205

FIGURE 12. Risk factors for CVE after kidney transplantation. Pretransplant and posttransplant factors conferring increased cardiovascular risk after kidney transplantation. CHF, congestive heart failure; CV, cardiovascular; LVH, left ventricular hypertrophy; PTDM, posttransplantation diabetes mellitus. Reprinted with permission from Stoumpos S, Jardine AG, Mark PB. Cardiovascular morbidity and mortality after kidney transplantation. Transpl Int. 2015;28:10–21.292

FIGURE 10. Screening and management of kidney transplant recipients for BKV replication and PVAN. BKV, BK virus; EM, electron microscopy; IVIG, intravenous immunoglobulin. Reprinted with permission from Hirsch HH, Randhawa P. BK polyomavirus in solid organ transplantation. Am J Transplant. 2013;13(Supp. 4):179–188.211

Full text

University of Birmingham
Practical Recommendations for Long-term
Management of Modifiable Risks in Kidney and
Liver Transplant Recipients
Neuberger, James; Bechstein, Wolf O; Kuypers, Dirk R J; Burra, Patrizia; Citterio, Franco; De
Geest, Sabina; Duvoux, Christophe; Jardine, Alan G; Kamar, Nassim; Krämer, Bernhard K;
Metselaar, Herold J; Nevens, Frederik; Pirenne, Jacques; Rodríguez-Perálvarez, Manuel L;
Samuel, Didier; Schneeberger, Stefan; Serón, Daniel; Truneka, Pavel; Tisone, Giuseppe; van
Gelder, Teun
DOI:
10.1097/TP.0000000000001651
License:
Creative Commons: Attribution-NonCommercial-NoDerivs (CC BY-NC-ND)
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Publisher's PDF, also known as Version of record
Citation for published version (Harvard):
Neuberger, J, Bechstein, WO, Kuypers, DRJ, Burra, P, Citterio, F, De Geest, S, Duvoux, C, Jardine, AG, Kamar,
N, Krämer, BK, Metselaar, HJ, Nevens, F, Pirenne, J, Rodríguez-Perálvarez, ML, Samuel, D, Schneeberger, S,
Serón, D, Truneka, P, Tisone, G & van Gelder, T 2017, 'Practical Recommendations for Long-term Management
of Modifiable Risks in Kidney and Liver Transplant Recipients: A Guidance Report and Clinical Checklist by the
Consensus on Managing Modifiable Risk in Transplantation (COMMIT) Group', Transplantation, vol. 101, no.
4S, pp. S1-S56. https://doi.org/10.1097/TP.0000000000001651
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Practical Recommendations for Long-term
Management of Modifiable Risks in Kidney
and Liver Transplant Recipients: A Guidance
Report and Clinical Checklist by the Consensus
on Managing Modifiable Risk in Transplantation
(COMMIT) Group
James M. Neuberger, MD, FRCP,
1
Wolf O. Bechstein, MD, PhD,
2
Dirk R.J. Kuypers, MD, PhD,
3
Patrizia Burra, MD, PhD,
4
Franco Citterio, MD, FEBS,
5
Sabina De Geest, PhD, RN,
6,7
Christophe Duvoux, MD, PhD,
8
Alan G. Jardine, MD, FRCP,
9
Nassim Kamar, MD, PhD,
10
Bernhard K. Krämer, MD,
11
Herold J. Metselaar, MD, PhD,
12
Frederik Nevens, MD, PhD,
13
Jacques Pirenne, MD, MSc, PhD,
14
Manuel L. Rodríguez-Perálvarez, MD, PhD,
15
Didier Samuel, MD, PhD,
16
Stefan Schneeberger, MD,
17
Daniel Serón, MD, PhD,
18
Pavel Trunečka, MD, PhD,
19
Giuseppe Tisone, MD,
20
and Teun van Gelder, MD, PhD
21
Abstract: Short-term patient and graft outcomes continue to improve after kidney and liver transplantation, with 1-year survival
rates over 80%; however, improving longer-term outcomes remains a challenge. Improving the function of grafts and health of re-
cipients would not only enhance quality and length of life, but would also reduce the need for retransplantation, and thus increase
the number of organs available for transplant. The clinical transplant community needs to identify and manage those patient mod-
ifiable factors, to decrease the risk of graft failure, and improve longer-term outcomes.
COMMIT was formed in 2015 and is composed of 20 leading kidney and liver transplant specialists from 9 countries across
Europe. The group’s remit is to provide expert guidance for the long-term management of kidney and liver transplant patients, with
the aim of improving outcomes by minimizing modifiable risks associated with poor graft and patient survival posttransplant.
The objective of this supplement is to provide specific, practical recommendations, through the discussion of current evidence and
best practice, for the management of modifiable risks in those kidney and liver transplant patients who have survived the first post-
operative year. In addition, the provision of a checklist increases the clinical utility and accessibility of these recommendations, by
offering a systematic and efficient way to implement screening and monitoring of modifiable risks in the clinical setting.
(Transplantation 2017;101: S1–S56)
Received 14 October 2016. Revision received 21 December 2016.
Accepted 6 January 2017.
1
Liver Unit, Queen Elizabeth Hospital Birmingham, United Kingdom.
2
Department of General and Visceral Surgery, Frankfurt University Hospital and
Clinics, Germany.
3
Department of Nephrology and Renal Transplantation, University Hospitals
Leuven, Campus Gasthuisberg, Belgium.
4
Department of Surgery, Oncology, and Gastroenterology, Padova University
Hospital, Padova, Italy.
5
Renal Transplantation Unit, Department of Surgical Science, Università Cattolica
Sacro Cuore, Rome, Italy.
6
Department of Public Health, Faculty of Medicine, Institute of Nursing Sci-
ence, University of Basel, Switzerland.
7
Department of Public Health, Faculty of Medicine, Centre for Health Services and
Nursing Research, KU Leuven, Belgium.
8
Department of Hepatology and Liver Transplant Unit, Henri Mondor Hospital
(AP-HP), Paris-Est University (UPEC), France.
9
Department of Nephrology, University of Glasgow, United Kingdom.
10
Department of Nephrology and Organ Transplantation, CHU Rangueil, Université
Paul Sabatier, Toulouse, France.
11
Vth Department of Medicine & Renal Transplant Program, University Hospital
Mannheim, University of Heidelberg, Mannheim, Germany.
12
Department of Gastroenterology and Hepatology, Erasmus MC, University
Hospital Rotterdam, the Netherlands.
13
Department of Gastroenterology and Hepatology, University Hospitals KU
Leuven, Belgium.
14
Abdominal Transplant Surgery, Microbiology and Immunology Department,
University Hospitals KU Leuven, Belgium.
15
Department of Hepatology and Liver Transplantation, Reina Sofía University
Hospital, IMIBIC, CIBERehd, Spain.
16
Hepatobiliary Centre, Hospital Paul-Brousse (AP-HP), Paris-Sud University,
Université Paris-Saclay, Villejuif, France.
17
Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical
University, Austria.
Supplement
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Number 4 www.transplantjournal.com S1

S
olid organ transplantation has evolved from an experi-
mental procedure to an established treatment option
for many types of end-stage organ failure. Both patient and
graft outcomes are continuing to improve, and 1-year patient
and graft survival currently exceed 80%.
1,2
However, sur-
vival rates gradually decline over the long term. In kidney
transplant, 5- and 10-year graft survival rates in Europe are
77% and 56%, and for liver transplant, 64% and 54%
(Figures 1 and 2).
3,4
Although most European countries have seen an increase
in both living and deceased donation, transplantation is not
available to all who would benefit from the procedure, and
there is considerable morbidity and mortality for those
listed for transplant.
6
Therefore, maximizing long-term
graft survival and reducing the need for retransplantation
is paramount, not only in improv ing outcomes for the re-
cipients but also for those awaiting a graft. The improve-
ment in outcomes is predominantly due to reduction in
18
Nephrology Department, Hospital Vall d’Hebrón, Autonomous University of
Barcelona, Spain.
19
Transplant Center, Institute for Clinical and Experimental Medicine (IKEM), Prague,
Czech Republic.
20
Department of Experimental Medicine and Surgery, University of Rome Tor
Vergata, Italy.
21
Department of Hospital Pharmacy and Internal Medicine, Erasmus MC, the
Netherlands.
Disclosure and contributions: The concept of the Consensus On Managing
Modifiable risk In Transplantation (COMMIT) program arose from feedback
following the Astellas Pharmaceutical Europe Ltd-sponsored meeting ‘Advancing
Transplantation: New questions, New possibilities’ held at the Karolinska Institute
in Sweden in January 2015 (Transplantation. 2017;101:S1–S41). The authors
were approached by Astellas to discuss the practical implementation of evidence
and discussion from the meeting related to managing modifiable risk factors in
posttransplantation care.
COMMIT is an expert-led program. The authors formed a “consensus group” which
met at various times over a period of approximately 1 year to discuss the
development of a practical guidance document. Led by chairs, James Neuberger,
Wolf Bechstein and Dirk Kuypers, the group developed their own content for their
meetings, with editorial support from iS Health. Astellas had input into the
selection of the program members and the appointment of iS Health to support
the program. Astellas Pharma Europe Ltd has provided support in the form of
funding for the meeting expenses, secretariat services by iS Health, and
placement of the supplement (guidance report and checklist) in the journal
selected by the authors.
Expert comments and guidance provided in this supplement are based on the
clinical experience and independent opinion of the authors, and reference
published clinical trial data. Previously unpublished data that could not be
included, due to existing embargo policies or to protect intellectual property, have
been excluded from this guidance document. The unpublished data in this
document were included at the discretion of the authors as personal
communications. All authors had final editorial authority over the content and
approved the final version of this supplement before submission. Astellas has had
no influence or input into the content development of the document.
Astellas Pharma and associated companies developed, manufacture and supply
tacrolimus (tacrolimus hard capsules (Prograf™), tacrolimus prolonged-release
hard capsules (Advagraf™)). Prescribing information can be found on page S54.
Advagraf is not licenced for patients receiving allogeneic liver transplants in the
United States. Discussions of tacrolimus dosing protocols unsupported by the
Advagraf license recommendations are included based on the clinical opinion of
the authors and referenced to published data.
J.M.N. reports nonfinancial support from Astellas during the development of this
supplement; nonfinancial support and personal fees from Astellas, Novartis,
Intercept, Roche, outside of the submitted work. D.R.J.K. reports nonfinancial
support from Astellas during the development of this supplement; nonfinancial
support and personal fees from Astellas, Novartis, Roche, Pfizer, BMS, Chiesi,
Polyphor, Alexion, Opsona Therapeutics; grants from Astellas, Novartis and
Roche, outside of the submitted work. W.O.B. reports nonfinancial support from
Astellas during the development of this supplement; nonfinancial support and
personal fees from Amgen, Astellas, Celgene, Dansac, Integra, Johnson and
Johnson, LifeCell, Medupdate GmbH, Merck Serono, Novartis, Pharmacept,
Roche; grants from Astellas, Baxter, Novartis, Pfizer, outside of the submitted
work. P.B. reports nonfinancial support from Astellas during the development of
this supplement; nonfinancial support and personal fees from Astellas, Novartis,
Kedrion, Grifols, Biotest, Gilead, Alfa Wassermann, outside of the submitted work.
F.C. reports nonfinancial support from Astellas during the development of this
supplement; nonfinancial support and personal fees from Astellas, Novartis, BMS,
outside of the submitted work. S.D.G. reports nonfinancial support from Astellas
during the development of this supplement; grant support from Astellas, Novartis,
Roche and Sanofi, outside of the submitted work. C.D. reports nonfinancial support
from Astellas during the development of this supplement; nonfinancial support and
personal fees from Astellas, Novartis, Chiesi; grants from Astellas, Novartis and
Roche, outside of the submitted work. A.G.J. reports nonfinancial support from
Astellas during the development of this supplement; nonfinancial support and per-
sonal fees from Astellas, Amgen, Novartis, Genzyme, Relypsa, AstraZeneca,
Boehringer Ingelheim, Bayer, Opsona Therapeutics; grants from Novartis, outside
of the submitted work. N.K. reports nonfinancial support from Astellas during the de-
velopment of this supplement; nonfinancial support and personal fees from Astellas,
Amgen, Novartis, Roche, Neovii, Sanofi; grants from Astellas, Novartis, outside of
the submitted work. B.K.K. reports nonfinancial support from Astellas during the de-
velopment of this supplement; nonfinancial support and personal fees from Amgen,
Astellas, Bayer, BMS, Chiesi, Hexal, Opsona Therapeutics, Pfizer, outside of the
submitted work. H.J.M. reports nonfinancial support from Astellas during the devel-
opment of this supplement; nonfinancial support and personal fees from Astellas,
Novartis, Intercept, Biotest; grants from Astellas, Biotest, Gilead, outside of the sub-
mitted work. F.N. reports nonfinancial support from Astellas during the development
of this supplement; nonfinancial support and personal fees from Centrale Afdeling
Fractionering (CAF), Intercept, Gore, BMS, Abbvie, Novartis, MSD, Janssen-Cilag,
Promethera Biosciences, Ono Pharma, Durect, Gilead; grants from Roche, Astellas,
Ferring, Novartis, Janssen-Cilag, Abbvie, outside of the submitted work. J.P. reports
nonfinancial support from Astellas during the development of this supplement;
nonfinancial support and personal fees from Astellas; grants from Astellas, Roche,
Centrale Afdeling Fractionering (CAF), Institut Georges Lopez (IGL), outside of the
submitted work. M.L.R.-P. reports nonfinancial support from Astellas during the de-
velopment of this supplement; nonfinancial support and personal fees from Astellas,
Novartis; grants from Astellas, outside of the submitted work. D.S. reports
nonfinancial support from Astellas during the development of this supplement;
nonfinancial support and personal fees from Astellas, Novartis, Biotest, Abbvie, Gil-
ead, Intercept, MSD, LFB; grants from Astellas, Novartis, Gilead, outside of the sub-
mitted work. S.S. reports nonfinancial support from Astellas during the development
of this supplement; outside of the submitted work: fees for Expert Groups/Advisory
Boards from Astellas, Novartis, Teva, Sandoz; fees for Steering Committees:
Astellas; unrestricted grants from Koehler Chemie, Novartis, Roche, Sandoz; travel
support: Astellas, Novartis, Roche, BMS. D.S. reports nonfinancial support from
Astellas during the development of this supplement; nonfinancial support and per-
sonal fees from Astellas, Novartis, Teva; grants from Astellas, Novartis, Teva,
Diaverum, outside of the submitted work. P.T. reports nonfinancial support from
Astellas during the development of this supplement; nonfinancial support and per-
sonal fees from Astellas, Novartis, Pfizer, outside of the submitted work. G.T. re-
ports nonfinancial support from Astellas during the development of this
supplement. T.vG. reports nonfinancial support from Astellas during the develop-
ment of this supplement; nonfinancial support and personal fees from Astellas,
Chiesi, Novartis, Teva; grants from Astellas, Chiesi, outside of the submitted work.
Correspondence: James M. Neuberger, MD, FRCP, Liver Unit, Queen Elizabeth
Hospital Birmingham, United Kingdom. (jamesneuberger@hotmail.co.uk).
Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. All rights
reserved. This is an open-access article distributed under the terms of the Creative
Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-
NC-ND), where it is permissible to download and share the work provided it is prop-
erly cited. The work cannot be changed in any way or used commercially without
permission from the journal.
ISSN: 0041-1337/17/10104-01
DOI: 10.1097/TP.0000000000001651
TX/16/0018/APEL March 2017.
S2 Transplantation
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Number 4 www.transplantjournal.com

early graft loss and patient death, better surgical and anes-
thetic skills, technological innovations, improved donor
and recipient management, and the advent of newer and
more effective immunosuppressive agents.
7
Despite the im-
provement in survival rates, attention is now becoming
more focused on improving longer-term outcomes beyond
the first year posttransplant.
Posttransplantation care requires involvement from multi-
disciplinary healthcare professionals (HCPs) who must work
collaboratively with the patient, their family , and the healthcare
FIGURE 1. 1- to 10-year graft and patient survival rates after kidney transplantation.
*
1-year and cumulative 5- and 10-year age-adjusted kid-
ney graft survival rates calculated for 2005 to 2008 by period analysis;
†
Survival probabilities were adjusted for age, sex and cause of end-stage
renal disease (data shown in figure for period 2004-2008);
‡
Data from 2007 to 2011 period not shown in figure. Figure based on data from
Gondos 2013 and Kramer 2016.
3,5
FIGURE 2. 1- to 10-year graft and patient survival rates in liver transplantation. Reprinted with permission of the European Liver Transplant
Registry: www.eltr.org/Evolution-of-LTs-in-Europe.html
4
(Accessed July 2016).
© 2017 Wolters Kluwer Neuberger et al S3

provider . Maintaining a viable graft and healthy patient in-
volves the consideration of many factors and balancing the need
for immunosuppression with the associated risks. In addition to
the direct and indirect consequences of immunosuppression,
a multitude of risk factors influence patient and graft sur-
vival. Some risk factors may be present before transplanta-
tion (such as cardiovascular disease (CVD) seen especially
in kidney transplant recipients), and other factors, such as
donor age, cannot be modified.
8,9
However, some risk fac-
tors have the potential to be modified or mitigated posttrans-
plantation to improve outcomes, including behavioral risk
factors, such as medication adherence.
10-12
The Consensus On Managing Modifiable risk In Trans-
plantation (COMMIT) group was convened to provide
practical recommendations for the identification and man-
agement of modifiable risk factors to maximize the life of
the graft and patient after kidney and liver transplant.
Modifiable Risk Factors for Graft
Loss Posttransplantation
Although solid organ transplantation improves both the
quality and quantity of life of the recipient, the survival is less
than an age-matched cohort from the general population. A
study in the United Kingdom of adult liver allograft recipi-
ents, who had survived the first postoperative year, showed
the average number of life-years lost was 7.7 years; those
who had their transplants at a younger age (17-34 years)
had a far greater loss of life-years than those who had their
transplant later (≥35 years), and women had fewer life-
years lost than men.
13,14
The main causes of death included
cardiac problems, malignancy, and infection, and causes of
graft failure included recurrent disease and chronic rejec-
tion.
15,16
In a retrospective review of 4483 adult primary
liver transplant recipients, major causes of death were malig-
nancy (30.6%), multisystem failure (10%), infection (9.8%),
graft failure (9.8%), and CVD (8.7%).
17
El-Agroudy et al
15
found the main causes of death in kid-
ney allograft recipients were infections (35.6%), CVD
(17.6%), liver disease (11.4%), and malignancy (6.1%). Of
nearly 1600 kidney recipients in Japan, Shimmura et al
16
found the main causes of death with a functioning graft were
infection (24%), stroke (17%), CVD (16%), malignancy
(15%), and liver failure (12%).
Graft loss has been attributed to both immunological and
nonimmunological factors in kidney and liver transplant re-
cipients (Figures 3 and 4).
Preoperative, perioperative, and postoperative factors may
impact long-term outcomes; these include donor and organ
factors as well as logistic factors. For kidney transplantation,
these include early ischemic injury, acute allograft rejection,
and delayed graft function (DGF). For liver transplanta-
tion, early allograft dysfunction (EAD), prolonged cold ische-
mia times and use of steatotic livers and organs from donation
after cardiac death (DCD) donors may contribute to reduced
graft and patient survival.
32-34
In both kidney and liver transplant recipients, modifiable
risk factors for graft failure over the longer term include is-
sues related to immunosuppression, such as nonadherence,
35
underimmunosuppression,
36
toxicity and adverse effects re-
lated to immunosuppression,
37
andhighintrapatientvariabil-
ity (IPV) in immunosuppressive exposure.
38
The development
of de novo donor-specific antibodies (DSAs) is also considered
to be a modifiable risk factor, and has been strongly associated
with nonadherence to immunosuppression in kidney trans-
plant recipients.
20
However, knowledge of the pathological
impact of DSAs is still evolving, particularly with regard to
the impact of DSAs postliver transplantation.
39-41
Furthermore, patient survival can be improved by atten-
tion to modifiable risk factors for CVD and cerebrovascular
disease, some infections and some cancers.
34
The develop-
ment of new-onset diabetes posttransplant (NODAT) is also
associated with reduced patient and graft survival, as well
as an increased risk of infections and CVD.
42
This list of risk
factors is not exhaustive. Other factors that may have an im-
pact on graft or patient survival include recurrence of initial
disease.
34
Although there is little to be done regarding the
nonmodifiable risk factors of graft failure, better screening
and management of modifiable risk factors could improve
long-term survival rates if integrated into routine clinical
practice. Each section in this guidance document includes a
review of the problem to be addressed, a summary of the lit-
erature and current clinical practice.
FIGURE 3. Causes of late graft loss in kidney transplant recipients. Figure based on data from Jevnikar 2008, Pazhayattil 2014, Sellarés 2012,
Lefaucheur 2010, Koenig 2016, Valenzuela 2013, Siedlecki 2011 and Puttarajappa 2012.
18-25
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Frequently asked questions

Q1. What contributions have the authors mentioned in the paper "University of birmingham practical recommendations for long-term management of modifiable risks in kidney and liver transplant recipients" ?

The group ’ s remit is to provide expert guidance for the long-termmanagement of kidney and liver transplant patients, with the aim of improving outcomes by minimizing modifiable risks associated with poor graft and patient survival posttransplant. The objective of this supplement is to provide specific, practical recommendations, through the discussion of current evidence and best practice, for themanagement of modifiable risks in those kidney and liver transplant patients who have survived the first postoperative year. 

Q2. What have the authors stated for future works in "University of birmingham practical recommendations for long-term management of modifiable risks in kidney and liver transplant recipients" ?

Although the future looks promising for the field of transplantation, recipients and HCPs must not lose sight of those factors that can be modified today, so leading to the best possible future outcomes for the recipients, and giving consolation to the donor family. 

Q3. What are the factors that affect the long-term outcomes of a kidney transplant?

perioperative, and postoperative factorsmay impact long-term outcomes; these include donor and organ factors as well as logistic factors. 

Q4. What is the risk factor for poor long-term graft survival?

Ischemia-reperfusion injury (IRI) is considered an unavoidable, but potentially modifiable, risk factor for poor long-term graft survival in solid organ transplantation. 

Q5. What are the main factors that may interfere with the metabolism and elimination of tacrolimus?

In liver transplantation, graft dysfunction and/or biliary complications may interfere with metabolism and elimination of tacrolimus. 

Q6. What is the effect of tacrolimus on trough concentrations?

The conversion from twice-daily to prolonged-release tacrolimus (capsules), both in kidney and liver transplant recipients, leads to lower blood trough concentrations and a reduced IPVof tacrolimus. 

Q7. What are some of the risk factors that can be modified after a transplant?

8,9 However, some risk factors have the potential to be modified or mitigated posttransplantation to improve outcomes, including behavioral risk factors, such as medication adherence. 

Q8. What is the cytolex ImmuKnow Cell Function Assay?

The Cylex ImmuKnow Cell Function Assay measures T-cell function by the release of adenosine triphosphate from CD4-positive lymphocytes in culture after a mitogenic stimulus. 

Q9. What is the role of CNIs and steroids in the development of hypertension in kidney transplant?

CNIs and steroids play a major role in the development of hypertension in kidney transplant patients; therefore, modifications of immunosuppressive regimen may be considered for lowering BP in these patients. 

Q10. What is the importance of maximizing long-term graft survival?

maximizing long-term graft survival and reducing the need for retransplantation is paramount, not only in improving outcomes for the recipients but also for those awaiting a graft. 

Q11. What is the average blood concentration in the liver and kidney transplant recipients?

During subsequent maintenance therapy, blood concentrations have generally been in the range of 5-15 ng/mL in liver and kidney transplant recipients. 

Q12. What is the reason for the large intrapatient and inter-subject exposure variability of tacrol?

the intrinsic pharmacokinetic and pharmacodynamic properties of tacrolimus, including erratic absorption, a variable first-pass effect, and unpredictable metabolism, may be responsible for its large intrapatient and inter-subject exposure variability. 

Q13. What was considered to be the advantages of having a lower burden?

161 For liver transplantation, historically, it was considered that there might be advantages to having a lower immunosuppressive burden. 

Q14. What is the reason for the increase in the use of CNI-based immunosuppressive?

Over the last 10 years, there has been a strong move in the renal transplant community to minimize CNI-based immunosuppressive regimens, largely based on reports of longterm nephrotoxicity. 

Q15. What is the evidence to support the conclusion that generics are safe?

There appears to be insufficient evidence to provide reassurance that, in transplanted patients, generics are therapeutically equivalent to innovator immunosuppressants.