The document discusses various immunosuppressive medications used for organ transplantation. It describes the standard medications used historically including total body irradiation, steroids, azathioprine, cyclosporine, and monoclonal antibodies. More recent immunosuppressants introduced between 1990-2000 include tacrolimus, mycophenolate mofetil, basiliximab, cyclosporine microemulsion, and daclizumab. Induction agents discussed include antithymocyte globulin, basiliximab, daclizumab, muromonab-CD3, alemtuzumab, and rituximab. Maintenance agents described are tacrolimus, cyclosporine, mycophenol
Steroid Sparing Regimens in Kidney TransplantationAbdullah Ansari
Mechanisms of action of steroids
Rationale for steroids minimization
Steroid minimization strategies
Very low maintenance dosages
Complete withdrawal early after transplantation (three to six months post-surgery)
Complete withdrawal later after transplantation (six months to one year post-surgery)
Steroid free maintenance, after rapid withdrawal within a week
Complete avoidance
ABO Incompatible Kidney Transplantation, Michael Casey, MD (W-0007)UF Nephrology
Welcome to the Division of Nephrology, Hypertension, & Renal Transplantation within the Department of Medicine at the University of Florida. The University of Florida is an exciting academic community filled with people passionate in their academic pursuit. The Division of Nephrology, Hypertension, & Renal Transplantation is distinguished by the impact, breadth, and depth of its clinical, training, and research programs. It is the Highest ranked Division of Nephrology within Florida, 13th top program nationally, and is comprised of distinguished faculty, all of whom are involved in patient care, research and education. Our research interests include cutting edge research and collaborations with Departments throughout the University.
For CME Credit, visit our website to register and complete the necessary requirements.
http://nephrology.medicine.ufl.edu
Immunosuppressants are drugs or medicines that lower the body's ability to reject a transplanted organ. Another term for these drugs is anti-rejection drugs. There are 2 types of immunosuppressants: Induction drugs: Powerful ntirejection medicine used at the time of transplant Maintenance drugs: Antirejection medications used for the long term.
Steroid Sparing Regimens in Kidney TransplantationAbdullah Ansari
Mechanisms of action of steroids
Rationale for steroids minimization
Steroid minimization strategies
Very low maintenance dosages
Complete withdrawal early after transplantation (three to six months post-surgery)
Complete withdrawal later after transplantation (six months to one year post-surgery)
Steroid free maintenance, after rapid withdrawal within a week
Complete avoidance
ABO Incompatible Kidney Transplantation, Michael Casey, MD (W-0007)UF Nephrology
Welcome to the Division of Nephrology, Hypertension, & Renal Transplantation within the Department of Medicine at the University of Florida. The University of Florida is an exciting academic community filled with people passionate in their academic pursuit. The Division of Nephrology, Hypertension, & Renal Transplantation is distinguished by the impact, breadth, and depth of its clinical, training, and research programs. It is the Highest ranked Division of Nephrology within Florida, 13th top program nationally, and is comprised of distinguished faculty, all of whom are involved in patient care, research and education. Our research interests include cutting edge research and collaborations with Departments throughout the University.
For CME Credit, visit our website to register and complete the necessary requirements.
http://nephrology.medicine.ufl.edu
Immunosuppressants are drugs or medicines that lower the body's ability to reject a transplanted organ. Another term for these drugs is anti-rejection drugs. There are 2 types of immunosuppressants: Induction drugs: Powerful ntirejection medicine used at the time of transplant Maintenance drugs: Antirejection medications used for the long term.
Immunosupuression in adult liver transplantation Abhishek Yadav
Basics about immunosuppressive drugs in liver transplantation and protocols for immunosuppression in adult liver transplantation. Discusses the basic immunology of transplant, common drugs and protocols used in special scenarios in transplantation.
Precision medicine is a rapidly growing field of medicine that proposes individually customized diagnostics and therapeutics based upon molecular and genetic profile of individual patients. The main goal of precision medicine is to minimize harmful side effects and maximize benefits. In particular, hematological malignancies were seen as the most direct candidates of the most promising applications of precision medicine. However, Precision medicine approaches face multiple challenges. Despite these challenges and limitations, continuous effort is carried out to use these molecular findings as disease biomarkers and targets for therapeutic intervention. In the last decade the hemato-oncology witnessed a major revolution in the understanding of the molecular pathogenesis of hematological malignancies. While the therapeutic research for hematologic malignancies is continuously expanding, some medicines have been approved in hematological malignancies patients’ therapeutic algorithm and many are still under investigation.
Medical Technology Tackles New Health Care Demand - Research Report - March 2...pchutichetpong
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According to Chris Mouchabhani, Managing Partner at M Capital Group, “Despite all economic scenarios that one may consider, beyond overall economic shocks, medical technology should remain one of the most promising and robust sectors over the short to medium term and well beyond 2028.”
There is a movement towards home-based care for the elderly, next generation scanning and MRI devices, wearable technology, artificial intelligence incorporation, and online connectivity. Experts also see a focus on predictive, preventive, personalized, participatory, and precision medicine, with rising levels of integration of home care and technological innovation.
The average cost of treatment has been rising across the board, creating additional financial burdens to governments, healthcare providers and insurance companies. According to MCG, cost-per-inpatient-stay in the United States alone rose on average annually by over 13% between 2014 to 2021, leading MedTech to focus research efforts on optimized medical equipment at lower price points, whilst emphasizing portability and ease of use. Namely, 46% of the 1,008 medical technology companies in the 2021 MedTech Innovator (“MTI”) database are focusing on prevention, wellness, detection, or diagnosis, signaling a clear push for preventive care to also tackle costs.
In addition, there has also been a lasting impact on consumer and medical demand for home care, supported by the pandemic. Lockdowns, closure of care facilities, and healthcare systems subjected to capacity pressure, accelerated demand away from traditional inpatient care. Now, outpatient care solutions are driving industry production, with nearly 70% of recent diagnostics start-up companies producing products in areas such as ambulatory clinics, at-home care, and self-administered diagnostics.
CHAPTER 1 SEMESTER V PREVENTIVE-PEDIATRICS.pdfSachin Sharma
This content provides an overview of preventive pediatrics. It defines preventive pediatrics as preventing disease and promoting children's physical, mental, and social well-being to achieve positive health. It discusses antenatal, postnatal, and social preventive pediatrics. It also covers various child health programs like immunization, breastfeeding, ICDS, and the roles of organizations like WHO, UNICEF, and nurses in preventive pediatrics.
Navigating Challenges: Mental Health, Legislation, and the Prison System in B...Guillermo Rivera
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ICH Guidelines for Pharmacovigilance.pdfNEHA GUPTA
The "ICH Guidelines for Pharmacovigilance" PDF provides a comprehensive overview of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines related to pharmacovigilance. These guidelines aim to ensure that drugs are safe and effective for patients by monitoring and assessing adverse effects, ensuring proper reporting systems, and improving risk management practices. The document is essential for professionals in the pharmaceutical industry, regulatory authorities, and healthcare providers, offering detailed procedures and standards for pharmacovigilance activities to enhance drug safety and protect public health.
CRISPR-Cas9, a revolutionary gene-editing tool, holds immense potential to reshape medicine, agriculture, and our understanding of life. But like any powerful tool, it comes with ethical considerations.
Unveiling CRISPR: This naturally occurring bacterial defense system (crRNA & Cas9 protein) fights viruses. Scientists repurposed it for precise gene editing (correction, deletion, insertion) by targeting specific DNA sequences.
The Promise: CRISPR offers exciting possibilities:
Gene Therapy: Correcting genetic diseases like cystic fibrosis.
Agriculture: Engineering crops resistant to pests and harsh environments.
Research: Studying gene function to unlock new knowledge.
The Peril: Ethical concerns demand attention:
Off-target Effects: Unintended DNA edits can have unforeseen consequences.
Eugenics: Misusing CRISPR for designer babies raises social and ethical questions.
Equity: High costs could limit access to this potentially life-saving technology.
The Path Forward: Responsible development is crucial:
International Collaboration: Clear guidelines are needed for research and human trials.
Public Education: Open discussions ensure informed decisions about CRISPR.
Prioritize Safety and Ethics: Safety and ethical principles must be paramount.
CRISPR offers a powerful tool for a better future, but responsible development and addressing ethical concerns are essential. By prioritizing safety, fostering open dialogue, and ensuring equitable access, we can harness CRISPR's power for the benefit of all. (2998 characters)
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2. What are Immunosuppressants?
Immunosuppressants are drugs or medicines that lower
the body's ability to reject a transplanted organ. Another
term for these drugs is anti-rejection drugs.
There are 2 types of immunosuppressants:
• Induction drugs: Powerful antirejection medicine used
at the time of transplant
• Maintenance drugs: Antirejection medications used for
the long term.
3. Standard Immunosuppression
Kumar A, Shrestha BM (2016) Evolution of Immunosuppressive Agents in Renal
Transplantation: An Updated Review. Int J Stem Cell Res Transplant 04(3), 158-172.
4. History :
• The ability to prolong life by transplanting organs had
long been a dream of medical practitioners.
• Early efforts at transplantation were unsuccessful
because of inadequacies in surgical technique and lack of
fundamental knowledge of the immune system.
• The kidney was the first such organ to be successfully
transplanted.
• Initial attempts at immunosuppression were with total
body radiation, but all the patients died.
• Steroids alone were then used, also without success. 4
5. History:
1950’s
• First successful kidney transplant
• Total body irradiation for immunosuppression
• Steroids
1960’s
• Azathioprine
1970’s
• Polyclonal anitbodies – anti-lymphocyte globulin (now Atgam,
Thymoglobulin)
1980’s
• Cyclosporine (Sandimmune ), “triple drug therapy”
• Monoclonal antibody, OKT3 (Orthoclone ) in 1985
5
9. ATG : Types
• Preparation made by immunization of animals with
human lymphoid tissue
Rabbits ➠
• Thymoglobulin (Genzyme)
• Anti-T-lymphocyte immune globulin (ATG- Fresinius)
Horses ➠ ATGAM
• Several studies found that rATG was more effective in
preventing rejection and was associated with better graft
survival than ATGAM.
9
11. ATG: Mechanism of action
• Rapid T-cell depleting agent through complement-
dependent cell lysis in the blood compartment and
apoptotic cell death in the lymphoid tissues.
• Also modulates cell surface molecules that regulate T cell
activation as well as adhesion molecules and chemokine
receptors involved in leukocyte-endothelial interactions.
• Repopulation leads to expansion of specific T-cell subsets
that have been shown to exhibit regulatory suppressor
functions, such as CD8+CD57+CD28- T cells.
11
12. ATG : Dosage
• rATG are antibodies derived from rabbit sources which
are commonly used induction agents although they are
approved for corticosteroid resistant rejection.
• These antibodies are FDA approved for treatment of
acute rejection at dose of 1.5 mg/kg for 7-14 days,
• Reported induction doses range from 1-6 mg/kg per
dose over 1-10 days with a more typical regimen of 1.5
mg/kg for 3-5 days
12Kalluri HV, Hardinger KL. Current state of renal transplant immunosuppression:
Present and future. World J Transplant 2012; 2(4): 51-68
13. ATG : adverse effects
• Common adverse events include cytokine release
syndrome, leukopenia and thrombocytopenia.
13Kalluri HV, Hardinger KL. Current state of renal transplant immunosuppression:
Present and future. World J Transplant 2012; 2(4): 51-68
20. Basiliximab: IL-2 Antagonist
• BASILIXIMAB has high specificity to the alfa-chain of IL-2
receptor on the surface of T cells which act by blocking
activated lymphocytes.
• Basiliximab has the FDA’s approval for the prophylaxis of
acute organ rejection in patients with renal
transplantation when used as part of a triple
immunosuppressive regimen that includes CsA, MMF and
corticosteroids.
• Its use is recommended for other solid organ transplant
recipients, as well. 20Maravic-Stojkovic V, Stojkovic B, Peric M. Modern immunosuppressive agents
after heart transplantation. Curr Trend Cardiol. 2017;1(2):41-48.
21. Basiliximab : dose and mechanism
• Basiliximab is registered for intravenous administration
only, as a bolus or as infusion over 30 minutes.
• It should be administrated only two times: first dose 20
mg within 2 hours after starting surgery, and second dose
4 days after transplantation.
• These saturate receptors and prevent T lymphocytes from
replication, and also from activating the B cells, which are
responsible for the production of antibodies, which would
bind to the transplanted organ and stimulate an immune
response against the graft 21Maravic-Stojkovic V, Stojkovic B, Peric M. Modern immunosuppressive agents
after heart transplantation. Curr Trend Cardiol. 2017;1(2):41-48.
24. KHA-CARI guideline for
induction therapy
24KHA-CARI adaptation of the KDIGO Clinical Practice
Guideline for the Care of Kidney Transplant Recipients. 2012.
26. European Best Practice Guidelines(EBPG) for
induction therapy
26Nephrology Dialysis Transplantation, Volume 15, Issue suppl_7, 2 December
2000, Pages 60–63
28. DACLIZUMAB
Daclizumab: IL-2 antagonist: Humanized, 90% human
10% murine origin
• 1 mg/kg within 24 hours of KT plus additional 4 doses
of 1 mg/kg at a schedule of every 2 weeks after KT.
• Causes receptor saturation that lasts up to 120 days
• Daclizumab was “retired” from market by the
manufacturer at the end of 2009
• Basiliximab will remain the only IL-2RA in the market
28
31. MUROMONAB CD3 (OKT3)
• OKT3 is a murine monoclonal antibody directed against
the CD3 receptor.
• Inert T-cell , removed via opsonization/phagocytosis.
• A substantial T-cell loss could occur within the first few
hours after an initial dose.
• As T-cell fall, several T-cell derived cytokines (eg,TNF,
IL-2, and IFN-γ) are released into circulation.
• Dosage: 5mg iv bolus, daily for 10 days
31
ITS AN OLD MOLECULE NOT USED NOWADAYS
32. ALEMTUZUMAB
• Recombinant DNA-derived humanized monoclonal
antibody directed against CD52
• CD52 is present on all B- and T-cells macrophages, NK
cells
• Trigger antibody-dependent lysis of T cell
• FDA approved in refractory B cell chronic lymphocytic
leukemia treatment
• DOSING: 20-30 mg on the day of transplantation infused
4-8 hr (over peripheral line)
32
36. Rituximab
Rituximab is not licensed for use in renal transplantation, but is
used ‘off-label’ in a variety of situations
• As Induction therapy in compatible renal transplantation
• Induction/desensitization in antibody incompatible
transplantation
• ABO blood group incompatible transplantation
• HLAi renal transplantation
• Treatment for acute renal allograft rejection
• Chronic antibody mediated rejection (CAMR)
• PTLD 36
37. Rituximab
Rituximab is monoclonal antibody that targets the
CD20 antigen expressed on the surface of pre-B and
mature B-lymphocytes.
Upon binding to CD20, rituximab mediates B-cell lysis.
Possible mechanisms of cell lysis include :
1. Complement dependent cytotoxicity (CDC)
2. Antibody dependent cell mediated cytotoxicity
(ADCC).
3. Antibody induced apoptosis 37
41. Calcineurin inhibitors
• Tacrolimus
• Cyclosporine
Vital role in:
• Post-transplant immunosuppressive regimens
• Solid organ post-transplant care for prevention of
acute rejection
• Prolonging and graft survival.
41
42.
43. MOA :Difference From CyA
• Although both tacrolimus
and CyA inhibit calcineurin
however inhibition is
achieved via complex
formation with different
binding proteins
(immunophilins).
• CyA binds with cyclophilin
and tacrolimus binds with
FKBP-12
45. MYCOPHENOLATE MOFETIL
• Mycophenolate mofetil
(MMF) is the synthetic
morpholino ethyl ester
prodrug of mycophenolic
acid (MPA), a natural
fermentation product of
several Penicillium species.
• MMF acts as an
antimetabolite
immunosuppressant. 45
46. Dosage in renal transplant
• Adults: A dose of 1 g administered orally twice a day
(daily dose of 2 g) is recommended for use in renal
transplant patients.
• Although a dose of 1.5 g administered twice daily (daily
dose of 3 g) was used in clinical trials and was shown to
be safe and effective, no efficacy advantage could be
established for renal transplant patients.
• Patients receiving 2 g/day of MMF demonstrated an
overall better safety profile than did patients
receiving 3 g/day of MMF.
47. Dosage in renal transplant
Pediatrics (3 months to 18 years of age)
• Patients with a body surface area of 1.25 m to 1.5 m2
may be dosed with MMF tablet at a dose of 750 mg
twice daily (1.5 g daily dose).
• Patients with a body surface area >1.5 m2 may be
dosed with MMF capsules or tablets at a dose of 1 g
twice daily (2 g daily dose).
48. Dosage in liver and heart
transplant
• A dose of 1.5 g bid oral (daily dose of 3 g)
is recommended for use in adult liver or
cardiac transplant patients.
MMF to be administered on an empty stomach. However, in stable
renal transplant patients, MMF may be administered with food if
necessary.
49. MYCOPHENOLATE SODIUM VS.
MYCOPHENOLATE MOFETIL
Characteristic Mycophenolate sodium Mycophenolate Mofetil
Absorption Small intestine Stomatch
Time to reach peak plasma
concentration (C-max)
1.5-2 hours 0.8-1.8 hours
MPA C-max 13.9 μg/ml at 14 days post renal
transplant
11.6 μg/ml at 14 days post renal
transplant
AUC (0-24 Hour) 29.1 μg/ml 23.3 ugh/ml
Dose 720 mg BID 1000 mg BID
Elimination half life 8-16 hours 16-18 hours
Adverse drug reactions GI SIDE EFFECTS LESS GI SIDE EFFECT VERY
COMMON
Saudi J Kidney Dis Transplant 2005;16(2):140-
50. LIMITATIONS WITH
CALCINEURIN INHIBITORS
• Mainstays of modern immunosuppression in renal
transplantation, but contribute significantly to the
chronic graft loss and the high morbidity and mortality
due to deleterious effects on renal graft,
cardiovascular profile and malignancies.
• Reduces acute rejection rates and improves short-term
graft survival, but they cause nephrotoxicity and death
with a functioning graft.
51. MTOR INHIBITORS
• mTOR inhibitors have a number of characteristics that
make them attractive for the use in Kidney Transplant:
a)Ability to prevent renal graft dysfunction
b)Reduction of angiogenesis;
c)Reduction of tumour growth and in de novo neoplasms;
d)Cardioprotective effects;
e)Reduction of viral infections
Nefrologia. 2017;37(3):253–266
53. DIFFERENCE BETWEEN
EVEROLIMUS AND SIROLIMUS
• Both everolimus and sirolimus have similar chemical
structures but PK differs.
• Half-life of everolimus (28 h) is considerably shorter than
that of sirolimus (62 h) and, everolimus reaches steady
state in 4 days, compared with 6 days for sirolimus.
• The onset of palpebral and lower limb oedema has been
associated with the use of both sirolimus and everolimus,
although some studies suggest that it is less frequent
with everolimus.
Nefrologia. 2017;37(3):253–266
54. MECHANISM OF ACTION
• Mtor inhibitors (sirolimus,
everolimus) resembles to
Tacrolimus but binds to
same intracellular FK binding
proteins.
• The drug inhibits
substantially T and B cell
proliferation.
55. FOUR STRATEGIES FOR THE USE OF
EVEROLIMUS IN KIDNEY
TRANSPLANT
1. The use with reduced-dose CNI in de novo KT
2. Preventive introduction of mTOR inhibitors with
withdrawal or minimisation of CNI at some point
of the KT in the absence of a clinical requirement
3. Conversion from CNI to everolimus in response to
certain clinical circumstances
4. CNI-free mTOR inhibitor regimen since the time
of KT
Nephrol Dial Transplant (2006) 21 [Suppl 3]: iii18–iii23
One of the most attractive aspects of the combined use of mTOR inhibitors with
CNIs is that the same immunosuppressive efficacy of each agent is obtained but
at lower doses.
56. WHY EVEROLIMUS SHOULD BE
ADMINISTRATED AFTER WOUND
HEALING?
• Inhibition of the mTOR pathway
limits cell proliferation and
angiogenesis of endothelial cells
and fibroblasts, and therefore it
may delay the fibrotic component
necessary for wound healing and
the re-canalisation of lymphatic
vessels.
57. PROPOSED PROTOCOL TO START
IMMUNOSUPPRESSION THERAPY USING
REDUCED-DOSE CNI AND DE NOVO
EVEROLIMUS
58. EVEROLIMUS DOSE
• Kidney transplantation: starting oral dose of 0.75 mg
twice daily as soon as possible after transplantation.
• Liver transplantation: starting oral dose of 1.0 mg
twice daily starting 30 days after transplantation.
• Monitor everolimus concentrations: Adjust maintenance
dose to achieve trough concentrations within the 3-8
ng/mL target range
• Administer consistently with or without food at the same
time as cyclosporine or tacrolimus
59.
60. AZATHI0PRINE
• Immunosuppressive
antimetabolite, is available in
tablet form for oral
administration and 100-mg
vials for intravenous
injection
• Prodrug that releases 6-
mercaptopurine
• First immunosuppressive
agent to achieve widespread
use in organ transplantation
61. CORTICOSTEROIDS
• Since the early 1960’s, corticosteroids were used in kidney
transplantation both as maintenance agents and to treat
acute rejections.
• Corticosteroids down-regulate cytokine gene expression
through interference with transcription. Since they are
lipophilic they first trans- locate into cytoplasm and bind to
receptors. The steroid –receptor complex then translocates
to the nucleus to bind to glucocorticoid responsive
elements on DNA to regulate transcription.
• By dampening cytokine production they blunt the immune
61
67. 1. Johnson C, Ahsan N, Gonwa T, et al. Randomized trial of tacrolimus (Prograf) in combination with azathioprine or mycophenolate mofetil
versus cyclosporine (Neoral) with mycophenolate mofetil after cadaveric kidney transplantation. Transplantation. 2000;69:834-841.
2. Gonwa T, Johnson C, Ahsan N, et al. Randomized trial of tacrolimus + mycophenolate mofetil or azathioprine versus cyclosporine +
mycophenolate mofetil after cadaveric kidney transplantation: results at three years. Transplantation. 2003;75:2048-2053.
68. 1. Johnson C, Ahsan N, Gonwa T, et al. Randomized trial of tacrolimus
(Prograf) in combination with azathioprine or mycophenolate mofetil
versus cyclosporine (Neoral) with mycophenolate mofetil after
cadaveric kidney transplantation. Transplantation. 2000;69:834-841
2. 2. Gonwa T, Johnson C, Ahsan N, et al. Randomized trial of tacrolimus
+ mycophenolate mofetil or azathioprine versus cyclosporine +
mycophenolate mofetil after cadaveric kidney transplantation: results at
three years. Transplantation. 2003;75:2048-2053
3. Ahsan N, Johnson C, Gonwa T et al. Randomized trial of tacrolimus
plus mycophenolate mofetil or azathioprine versus cyclosporine oral
solution (modified) plus mycophenolate mofetil after cadaveric kidney
transplantation: results at 2 years. Transplantation. 2001;72:245-250.
69. Steroid avoidance /Withdrawl
• Steroid withdrawal typically involves discontinuing
steroids several months post transplantation whereas
steroid avoidance involves no corticosteroid
maintenance at all and only a brief exposure to
steroids in the immediate post operative period.
• Studies demonstrate that early steroid withdrawal is
safer than late withdrawal as late withdrawal was
associated with increased risk of acute rejections.
69
70. Land Mark Trials for Steroid avoidance
/Withdrawl (SAW)
• A recent meta-analysis of 34 randomized controlled studies using SAW
regimens published by Knight et al concluded that SAW is associated with
increased risk of acute rejection, however this did not impact long term
patient or graft survival.
• There is a more favorable cardiovascular profile with SAW most likely
secondary to decreased incidence of hypertension, new onset diabetes
and dyslipidemia.
• It is generally implemented with caution in high immunologic risk
recipients (high PRA, repeat transplants, young recipients, patients with
prior rejections and/or unstable graft function).
• With use of more potent induction regimens more US centers are
currently implementing SAW in immunologically low risk recipients.
70Overview of Immunosuppression in Renal Transplantation
http://dx.doi.org/10.5772/54865
71. KDIGO recommendations for Maintainance
Immunosuppression
• 2.1: We recommend using a combination of
immunosuppressive medications as maintenance therapy
including a CNI and an antiproliferative agent, with or
without corticosteroids. (1B)
• 2.2: We suggest that tacrolimus be the first-line CNI
used. (2A)
• 2.2.1: We suggest that tacrolimus or CsA be started
before or at the time of transplantation, rather than
delayed until the onset of graft function. (2D tacrolimus;
2B CsA) 71
72. KDIGO recommendations for Maintainance
Immunosuppression
• 2.3: We suggest that mycophenolate be the first-line
antiproliferative agent. (2B)
• 2.4: We suggest that, in patients who are at low
immunological risk and who receive induction therapy,
corticosteroids could be discontinued during the first week
after transplantation. (2B)
• 2.5: We recommend that if mTORi are used, they
should not be started until graft function is
established and surgical wounds are healed.(1B)
72
73. KDIGO recommendations for long term
Maintenance Immunosuppression
• 3.1: We suggest using the lowest planned doses of
maintenance immunosuppressive medications by 2–4
months after transplantation, if there has been no acute
rejection. (2C)
• 3.2: We suggest that CNIs be continued rather than
withdrawn. (2B)
• 3.3: If prednisone is being used beyond the first week
after transplantation, we suggest prednisone be continued
rather than withdrawn. (2C)
73
74. KHA-CARI guideline for
maintenance therapy
74KHA-CARI adaptation of the KDIGO Clinical Practice
Guideline for the Care of Kidney Transplant Recipients. 2012.
75. KHA-CARI guideline for long term
maintenance therapy
a. We recommend low-level exposure to maintenance
immunosuppressive medications by 4 months after transplantation, as
was used in the Symphony Trial (Tacrolimus trough concentrations 3–7
ng/mL, mycophenolate 1–2 g daily and prednisone 5 mg daily) for
patients who have not experienced acute rejection. (1B)
b. We suggest that CNI be continued rather than withdrawn.(2B)
c. If prednisolone is being used beyond the first week after
transplantation, we suggest prednisolone be continued rather than
withdrawn. (2C)
75KHA-CARI adaptation of the KDIGO Clinical Practice
Guideline for the Care of Kidney Transplant Recipients. 2012.
77. European Best Practice Guidelines(EBPG) for
Maintenance therapy
77Nephrology Dialysis Transplantation, Volume 15, Issue suppl_7, 2 December
2000, Pages 63–67,
78. European Best Practice Guidelines(EBPG) for
Maintenance therapy
78Nephrology Dialysis Transplantation, Volume 15, Issue suppl_7, 2 December
2000, Pages 63–67,
79. European Best Practice Guidelines(EBPG) for
Maintenance therapy
79Nephrology Dialysis Transplantation, Volume 15, Issue suppl_7, 2 December
2000, Pages 63–67,
82. Newer Immunosuppression drugs
82
AGENT MECHANISM OF
ACTION
CLINICAL
INDICATION
TRIAL ONGOING
TOL101 Target ? T cell receptor
Non depletional
Inactivates T cell
Induction Phase 2
Sotrastaurin Protein kinase C
inhibitor
Blocks T - cell
activation
Maintenance Studies halted
secondary to
increased
rejection rates
Tofacitinib Inhibitor of the JAK -
STAT pathway.
Blocks T – cell
activation
Maintenance Phase 2
ASKP1240 Humanized antibody
against CD40 on
antigen
presenting cells
Maintenance Phase 1
83. Summary
83Hardinger KL, Brennan DC. Novel immunosuppressive agents in kidney transplantation. World J Transplant 2013; 3(4): 68-77