Prior to the start of the program, ensure you have the following printed program materials:

Prior to the start of the program, ensure you have the following printed program materials:•Syllabus

– Pre-activity Survey

• Located at the front of your syllabus– CME Evaluation with Post-activity Survey• Located at the back of your syllabus

DisclosuresDisclosures

• The relevant financial relationships reported by faculty that they or their spouse/partner have with commercial interests is located on page 5 of your syllabus

• The relevant financial relationships reported by the steering committee that they or their spouse/partner have with commercial interests is provided on page 5 of your syllabus

• The relevant financial relationships reported by the non-faculty content contributors and/or reviewers that they or their spouse/partner have with commercial interests is located on page 5 of your syllabus

Off-label Discussion DisclosureOff-label Discussion Disclosure

This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. PCME does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.

Educational ObjectivesEducational Objectives

• Examine the most recent data on kidney disease outcomes after liver transplantation, and identify criteria that are currently being investigated to guide patient selection for liver alone vs dual organ transplant

• Apply an up-to-date understanding of the mechanisms underlying antibody-mediated rejection to the initiation of evidence-based approaches to prevent rejection and minimize immunosuppressant-associated toxicity

• Identify strategies to maximize adherence in patients undergoing solid organ transplant

Pre-activity SurveyPre-activity Survey

• Please take out the Pre-activity Survey from your packet

• Your answers are important to us and will be used to help shape future CME activities

• It is important that you fill out the information at the top of the form:

– Please select the best answer(s) for the questions below:

– Degree: _MD/DO _ Nursing Professional _ PharmD _Other:_____________________________

– Specialty: _Hepatologist _Transplant Surgeon _ Nephrologist _Other:_____________________________

Pre-activity Survey Question 1Pre-activity Survey Question 1

How often do you think simultaneous liver/kidney (SLK) transplantation should be performed in non-ESRD patients needing a liver transplant?

A. >20% of the timeB. 10% to 19% of the timeC. 5% to 9% of the timeD. <5% of the time


Which of the following liver failure patients should generally not be given an SLK transplant?

A. ESRDB. Metabolic kidney disease C. No ESRD but receiving hemodialysis for 2 monthsD. Stage 4-5 CKD, with no proteinuria and 25% likelihood of

developing ESRD after liver transplant aloneE. All of the above are good candidates for SLKF. None of the above should be given a SLK


Liver transplant candidates with stage 4-5 chronic kidney disease (CKD) should be receiving an SLK?

A. CorrectB. IncorrectC. I don’t know


Please rate your level of confidence in your ability to select a candidate for SLK:

1 2 3 4 5

Not confident Expert


Please rate your level of confidence in recognizing the signs and symptoms of antibody-mediated rejection (AMR):

1 2 3 4 5



In your practice, what percentage of your transplant patients almost never miss doses of their immunosuppressive medications one year after transplantation?

A. 75% to 100% of my patientsB. 25% to 74%C. 10% to 24%D. <10%E. I don’t know


What strategies have you implemented in your practice to address patient adherence (select all that apply)?

A. Education

B. Modify/simplify treatment regimen

C. Schedule office visits, even when the patient feels well

D. I have not implemented any strategy yet


A 60-year-old male with a history of type 2 diabetes mellitus (5-yr) and liver disease secondary to NASH is evaluated for liver transplantation. He has never been told he had kidney disease. Labs: Serum creatinine: 3.2 mg/dL (up from 1.2 mg/dL a year earlier, and 1.5 mg/dL 4 days ago); Urine output: 690 mL per day (down from 1.2 liters 4 days ago); Serum Na+ 129 mEq/L; Serum K+ 5.8 mEq/L; Urine: PCR 0.3 mg/g; Na+ 12 mEq/L.

Is this patient a dual liver/kidney transplant candidate?A. YesB. NoC. I don’t know


In liver transplant recipients with eGFR >30 mL/min/1.73 m2, compared to standard tacrolimus dosing, the addition of everolimus to reduced tacrolimus did which of the following:

A. Prevented kidney function loss but increased the incidence of acute rejection, graft loss, and death

B. Prevented kidney function loss with similar impact on the incidence of acute rejection, graft loss, and death

C. Similarly reduced kidney function and the incidence of acute rejection, graft loss, and death

D. I don’t know


The most common cause of AMR is?

A. Viral infection

B. Non-adherence to regimen

C. Age of recipient

Case ReportCase Report

• 62-year-old male with 5-year history of T2DM

• History of liver disease secondary to NASH

• Presented to local hospital with abdominal pain, nausea, and coffee ground emesis

• Transferred for liver transplant evaluation

• Work-up revealed decompensated liver failure; ultrasound showed a cirrhotic liver; EGD esophagitis with varices

Case Report: Laboratory FindingsCase Report: Laboratory Findings• Upon transfer, Cr 2.4 mg/dL

– On admission, Cr 1.5 mg/dL – 1 year earlier, Cr 0.6 mg/dL

• Urine output – 1.2 L at transfer– Over 3 days, decreased to 690 mL/day

• Patient became encephalopathic– Cr 3.2 mg/dL, Na+ 129 mEq/L, K+ 5.8 mEq/L

• Urinalysis bland– PCR 0.3 g/g, Urine Na+ 12 mEq/L

• Patient placed on active list for a liver transplant – MELD: 34

Case Report: Renal UltrasoundCase Report: Renal Ultrasound

Renal ultrasound showed mild echogenicity, but was otherwise normal

Figure 1A: normal Figure 1B: case

Photos courtesy of Dr. F. Vincenti.

Polling questionPolling question

Is this patient a dual liver/kidney transplant candidate?

1. Yes

2. No

3. I need more information

Consequences of MELD Allocation SystemConsequences of MELD Allocation System

• Intended– Reduced waitlist mortality

• Unintended– Livers often allocated on basis of kidney disease severity

– Compared to pre-MELD era:

• SLK listings have increased

• SLK transplants increased

Eason JD et al. Am J Transplant. 2008;8:2243-2251.Davis CL et al. Am J Transplant. 2007;7:1702-1709.

Abnormal Kidney Function is More Common in Liver Candidates in MELD Era Abnormal Kidney Function is More Common in Liver Candidates in MELD Era

Pre-OLT creat (mg/dl)

% ptspre-MELD

% ptspost-MELD

0-0.99 51.8 46.1 P<0.0001

1-1.99 36.6 38.5

≥ 2.0 7.9 10.0

Dialysis 3.7 5.3

Pre-MELD 1999-2002, n=11010; Post-MELD 2002-2004, n=13163, data from SRTR

Gonwa TA et al. Am J Transplant. 2006;6:2651-2659.

Increasing Number of SLK in USA in MELD EraIncreasing Number of SLK in USA in MELD Era

From 2012 Annual Report of OPTN/SRTR.

MELD introduced

% S

LK

# SL

K

Limited Utility of Estimating Equations in Candidates with eGFR <40 mL/min Limited Utility of Estimating Equations in Candidates with eGFR <40 mL/min

Method GFR<40 ml/min GFR>40 ml/min

# pts GFR # pts GFR

Iothalamate* 155 22.6 1218 99.4

Cockcroft-Gault 151 46.1 1213 85.5

Nankivell 148 58.0 1198 99.0

MDRD 4 155 44.5 1218 87.8

MDRD 5 155 43.9 1218 90.5

MDRD 6 155 39.0 1218 82.4

Gonwa TA et al. Liver Transpl. 2004;10:301-309.

1447 OLT recipients, 1984–2001; *iothalamate GFR used as “gold-standard”

Reasons That Centers Consider SLKReasons That Centers Consider SLK

• Avoid peri-operative dialysis

• Potential to prevent

– Non-recovery of pre-operative AKI

– Early post-transplant ESRD

– Subsequent ESRD and need for later kidney from another donor

• May protect center from risk of being exposed to poor outcomes based on LTA

Wide Variation in Simultaneous Liver-Kidney Transplants Between Regions Wide Variation in Simultaneous Liver-Kidney Transplants Between Regions

Nadim MK et al. Am J Transplant. 2012;12:3119-3127.

Polling QuestionPolling Question

Independent of eGFR, all of the following factors at the time of LTA have been associated with ESRD except:

1. Older age

2. Diabetes mellitus

3. Duration of dialysis

4. Presence of abnormalities on kidney biopsy


Independent of eGFR, all of the following factors at the time of LTA have been associated with ESRD except:

1. Older age

2. Diabetes mellitus

3. Duration of dialysis

4. Presence of abnormalities on kidney biopsy

Renal Criteria Used to Determine Need for SLK vs LTA in Liver CandidatesRenal Criteria Used to Determine Need for SLK vs LTA in Liver Candidates

AKI: minimum duration of dialysis for determining SLK

% of respondents

4 weeks 32%

6 weeks 37%

8 weeks 32%

CKD (GFR)

GFR <40 ml/min 24%

GFR <30 ml/min 76%

Survey of 88 centers that perform SLK, 65% responseResults of National Survey of US Transplant Centers

Nadim MK et al. Am J Transplant. 2012;12:3119-3127.

Risk of ESRD After LTA in Patients with Fluctuating eGFR Pre-transplantRisk of ESRD After LTA in Patients with Fluctuating eGFR Pre-transplant

Ruebner R et al. Am J Transplant. 2012;12:2958-2965.

ESRD by 6 Months Post-LTA and Pre-transplant Acute Dialysis DurationESRD by 6 Months Post-LTA and Pre-transplant Acute Dialysis Duration

Sharma P et al. Clin J Am Soc Nephrol. 2013;8:1135-1142.

Predictors of Non-recovery of Kidney Function Post-LTAPredictors of Non-recovery of Kidney Function Post-LTA

Sharma P et al. Clin J Am Soc Nephrol. 2013;8:1135-1142.

Association of Pre-transplant Dialysis Duration and Survival After SLKAssociation of Pre-transplant Dialysis Duration and Survival After SLK

Adapted from Locke JE et al, Transplantation 2008

Duration of Dialysis (mos)

RR

of D

eath

*

Cox Proportional Hazard Analysis Comparing SLK and matched-control LTA recipients, matched for donor age, race, cause of death, recipient MELD and dialysis status

P=0.05, SLK vs LTA

Poor Outcomes in Elderly Patients on Dialysis at Time of Liver TransplantPoor Outcomes in Elderly Patients on Dialysis at Time of Liver Transplant

UNOS data, n=9877, MELD eraDellon ES et al. Am J Transplant. 2006;6:2183-2190.

>65, on dialysis

≥65, L<65, D, L <65, D, L/K

≥65, D, L<65, L≥65, D, L/K

Prop

ortio

n of

pat

ient

s su

rvivi

ng

Days post-transplantation

Distribution of LTA Patients Based on RIFLE Classification Distribution of LTA Patients Based on RIFLE Classification

• No AKI: 165

• Risk 34

• Injury 19

• Failure 65

– ATN 30

– HRS 35

Nadim MK et al. Liver Transpl. 2012;18:539-548.

• Retrospective, 283 pts• ATN based on clinical diagnosis

Recovery of Kidney Function After OLTRecovery of Kidney Function After OLT

Nadim MK et al. Liver Transpl. 2012;18:539-548.

Limitations with Comparing SLK and LTA Outcomes in MELD EraLimitations with Comparing SLK and LTA Outcomes in MELD Era

• Only retrospective studies

• Lack of:– Appropriate control groups

– Standardized selection criteria for SLK

– Pre-LTA kidney and/or dialysis data

– Data on pre-txp comorbidity

• Kidney outcomes after LTA not well characterized

• Misclassification with registry data

• Differences in liver disease severity?

Kidney Biopsy in Liver Transplant Candidates Kidney Biopsy in Liver Transplant Candidates • Pathological abnormalities common

• High risk of bleeding complications

• Not shown to be better than serum creatinine in predicting:

– Post-txp reversibility

– Post-txp kidney function

– Rate of decline of GFR

– Time to ESRD

• Should be considered a research tool for nowMcGuire BM et al. Ann Intern Med. 2006;144:735-741.Wadei HM et al. Am J Transplant. 2008;8:2618-2626.Tanriover B et al. Transplantation. 2008;86:1548-1553.

OPTN Policy ProposalOPTN Policy Proposal

Listing Criteria for SLK

a.ESRD

b.CKD with GFR <30 (MDRD-6 or iothalamate) and proteinuria >3 g/day

c.Sustained AKI requiring dialysis for >6 weeks

d.Sustained AKI (GFR <25) for >6 weeks not on dialysis

e.Sustained AKI: combination of time in (c) and (d) >6 weeks

f. Metabolic disease

OPTN Kidney Transplantation Committee and the Liver and Intestinal Organ Transplantation Committee (OPTN Policy 3.5.10).

OPTN Policy ProposalOPTN Policy Proposal

Priority local listing for KAL• If listed for SLK but received LTA

OR• If required 2 weeks of pre-LTA dialysis and/or eGFR 30-40

mL/min for 4 weeks pre-LTA

ANDa.Continued maintenance dialysis for >90 days post-LTA

b.non-recoverable kidney function

c.between 90-180 days post-LTA

OPTN Kidney Transplantation Committee and the Liver and Intestinal Organ Transplantation Committee (OPTN Policy 3.5.10 and 3.5.10.1).

SLK Allocation in MELD Era Summary of IssuesSLK Allocation in MELD Era Summary of Issues

• Inadequate characterization of pre-kidney function has limited the establishment of uniform criteria

• 3 months duration of severe kidney disease is tipping point for worse outcomes after LTA

• CKD defined by impaired kidney function for >3 months

• Should restrict SLK to patients with stage 4-5 CKD

– No clear benefit for patients not on dialysis

– Selects patients with lowest likelihood of renal recovery

Proposed Algorithm: SLK vs LTA in Liver Candidates with Kidney DysfunctionProposed Algorithm: SLK vs LTA in Liver Candidates with Kidney Dysfunction

Bloom RD et al. Adv Chronic Kidney Dis. 2009;16:268-277.

Case Report: Liver TransplantCase Report: Liver Transplant

• Transplant nephrology consulted to initiate CRRT

• Decision made that patient did not require kidney transplant

• Patient had a GI bleed requiring multiple transfusions; transferred to ICU

• CRRT initiated

• Urine Na <10 mEq/L; urine output decreased to 200-300 mL

• 6 days later, underwent OLT

• Continued on CVVHD for 48 hours

• Remained oliguric on steroids and mycophenolate mofetil for 5 days, then started on tacrolimus 2 mg bid

• Discharged, eGFR 20mL/min


In LTA with GFR <25mL/min, which would you NOT consider?

1.Continue the present immunosuppressive regimen

2.Reduce the dose of tacrolimus

3.Convert tacrolimus to mTor


In LTA with GFR <25mL/min, which would you NOT consider?

1.Discontinue tacrolimus

2.Reduce the dose of tacrolimus

3.Convert tacrolimus to mTor

Everolimus in Liver TransplantEverolimus in Liver Transplant

Saliba F et al. Am J Transplant. 2013;13:1734-1745.

Everolimus in Liver TransplantEverolimus in Liver Transplant

Saliba F et al. Am J Transplant. 2013;13:1734-1745.

Case Report: Post-liver TransplantationCase Report: Post-liver Transplantation

• 9 months post-liver transplant, kidneys failed and patient received a kidney transplant from his 33-year-old son

• T and B cell cytotoxicity crossmatches were negative

• Kidney functioned immediately

• At 1 month, Cr 1.3 mg/dL; on steroids, mycophenolate mofetil and tacrolimus

Case Report: Post-liver TransplantationCase Report: Post-liver Transplantation

• At 3 months, Cr increased to 2.5 mg/dL

• Biopsy revealed Type Ib Banff acute T cell rejection; thymoglobulin begun

• Cr remained at 1.8 mg/dL

• Patient did not return for follow-up; compliance concerns

• Presented 9 months later complaining of fatigue and edema; Cr 2.6 mg/dL, a urine PCR 1.2 mg/g

Case Report: BiopsyCase Report: Biopsy

Figure 2A Figure 2B

Figure 2C Figure 2D

Photos courtesy of Dr. F. Vincenti.

Case ReportCase Report

• Blood sample sent for DSA

– Moderate risk antibodies to the donor HLA DQ3 (7000 MFI)


What is the most common cause of AMR?

1. Viral infection

2. Non-adherence to regimen

3. Age of recipient


What is the most common cause of AMR?

1. Viral infection

2. Non-adherence to regimen

3. Age of recipient

Other Causes6 (11%)

Other Causes6 (11%)

Glomerulonephritis10 (18%)

Glomerulonephritis10 (18%)

BK Virus4 (7%)

BK Virus4 (7%)

Antibody-MediatedRejection 36 (64%)Antibody-MediatedRejection 36 (64%)

Nonadherent17 (47%) Adherent

19 (53%)

Causes of Kidney Transplant FailureCauses of Kidney Transplant Failure

Sellares J et al. Am J Transplant. 2012;12:388-399.

Early (<3 Months) vs Late Acute AMR after Kidney TransplantEarly (<3 Months) vs Late Acute AMR after Kidney Transplant

Dörje C et al. Transplantation 2013;96:79-84.

C1q Complement-binding Anti-HLA abC1q Complement-binding Anti-HLA ab

• 1,016 allograft kidney transplants recipients

• Five-year survival of the transplanted kidney: – 54% in patients with C1q anti-HLA ab

– >93% in those with non-complement binding anti-HLA antibodies and those without donor-specific anti-HLA antibodies (P<0.001)

• AMR was the cause of rejection in 48% patients with C1q anti-HLA ab (vs 16% of patients without)

Loupy A et al. N Engl J Med. 2013;369:1215-1226.

KDIGO Guideline Recommendation for Treatment of Acute AMR KDIGO Guideline Recommendation for Treatment of Acute AMR

6.4: We suggest treating antibody-mediated acute rejection with one or more of the following alternatives, with or without corticosteroids (2C):

•plasma exchange;

•intravenous immunoglobulin;

•anti-CD20 antibody;

•lymphocyte-depleting antibody.

Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009;9:S21.

• Searched treatment of AMR with IVIG, monoclonal antibodies (rituximab or eculizumab), proteasome inhibitors (bortezomib), and plasmapheresis/exchange

• Studies published 1950 – March 2011

• MEDLINE, EMBASE, Cochrane, and meeting abstracts

• 5 randomized and 7 non-randomized controlled trials

• GRADE quality low or very low

Acute AMR Treatment after Kidney Transplant: A Systematic Review of Controlled Trials

Acute AMR Treatment after Kidney Transplant: A Systematic Review of Controlled Trials

Roberts DM et al. Transplantation. 2012;94:775-783.

1st Author Year

Inter- vention

NumberTreated/Con

Graft Failure Treated/Con Benefit?

Böhmig2007

Immuno-adsorption 5/5 0/4 Yes

Bonomini1985

Plasma-pheresis 23/21 7/17 Yes

Kirubakaran1981

Plasma-pheresis 12/12 6/3 No

Allen1983


Blake1990


Acute AMR Treatment after Kidney Transplant: Results of 5 RCTs

Acute AMR Treatment after Kidney Transplant: Results of 5 RCTs


Treatment of AMR after Kidney Transplant


Plasmapheresis

Immunoadsorption

IVIG

Bortezomib

Corticosteroids

Antithymocyte ab

Eculizumab

Mycophenolate

Rituximab

Cyclophosphamide

Deoxyspergualin

Splenectomy

Tacrolimus1972-76

2007-112002-06

1997-011992-96

1987-911982-86

1977-81

n=0

n=700



Treatment EvidencePlasmapheresis Low, benefit not consistentImmunoadsorption Low, seems beneficialIVIG Very lowBortezomib Very lowCorticosteroids Very lowAnti-thymocyte preparations Very lowEculuzamib Very lowMycophenolate Very lowRituximib Very lowCyclosphosphamide Very lowDeoxyspergualin Very lowSplenectomy Very lowTacrolimus Very low



“Data describing the efficacy of treatments for AMR in renal allografts are of low or very low quality. Larger randomized controlled trials and dose-

response studies are required.”


“Data describing the efficacy of treatments for AMR in renal allografts are of low or very low quality. Larger randomized controlled trials and dose-

response studies are required.”

Conservative Treatment of Early Mixed AMR

Sun Q et al. Kidney Int. 2007;71:24-30.

Day of Biopsy

Banff ’97 Grade

C4d/PTC

PMNs

ReceivedIL2-RA Before

CSA Before (ng/mL)

TAC Before (ng/mL)

TAC After

(ng/mL)

S Cr Before (mg/dL)

S Cr After

(mg/dL)

9 IIA +/+ Dac 10.9 10.0 4.17 0.886 IIB +/+++ -- 208 12.5 CVVH 1.006 IIB +/++ -- 186 14.5 6.97 1.567 IIA +/+ Dac NA 10.4 6.36 0.9410 IIB +/++ Bas 160 7.1 CVVH 0.9110 IIA +/+++ Bas 103 10.9 CVVH 0.966 IIA +/+ -- 176 9.1 4.79 1.378 IIB +/++ Bas 12.8 11.2 9.04 1.748 Brdrln +/+ -- 348 12.0 3.26 0.888 IB +/++ -- 5.7 9.2 CVVH 1.245 IIB +/+++ -- 8.3 9.5 CVVH 0.79

Conservative Treatment of Early Mixed AMR Conservative Treatment of Early Mixed AMR

Sun Q et al. Kidney Int. 2007;71:24-30.

Potential Treatments of AMR that Require Additional StudyPotential Treatments of AMR that Require Additional Study

• Intravenous immunoglobulin• Rituximab (B-cell antibody)• Bortezomib (proteasome inhibitor)• Eculizumab (C5 inhibition)• C1 Esterase Inhibitor• BAFF inhibitors• Plasmapheresis

Early AMR (n=40)

Late AMR (n=27)

Low drug levels 0/40 (0%) 15/27 (56%)*Low drug levels andnon-adherent 0/0 (0%) 10/15 (75%)

Age (y) 50.9±11.6 37.9±12.9*Age (y) of those that were non-adherent 26.6±9.5

*P<0.001 vs Early AMR

Early vs Late Acute AMR Role of Non-adherenceEarly vs Late Acute AMR Role of Non-adherence

Dörje C et al. Transplantation. 2013;96:79-84.

Addressing Late Graft LossAddressing Late Graft Loss

• Shift in thinking about the causes of late graft rejection: insufficient immunosuppression and non-adherence to immunosuppressive medication are key factors.

• Insufficient immunosuppression may occur during immunosuppressive minimization (tapering) or calcineurin-inhibitor-avoidance

• Patients at high risk for non-adherence, specifically young adults who are in the transition phase from pediatric to adult renal services, should be identified.

Morath et al. Special Issue: Special Focus – Antibody-Mediated Rejection. Transpl Int. 2012;25:633-645.

Increasing Adherence in Transplant PatientsIncreasing Adherence in Transplant Patients

• Adherence to immunosuppressant regimens is challenging– Patients commonly take >8 medications/day at multiple specific times– Weekly clinic appointments for ~1 year post-transplantation– Laboratory visits between clinic visits– Significant lifestyle changes to incorporate healthy behaviors

• Physicians and other members of the transplant team can help improve adherence by providing education on treatment expectations, management of side effects, and strategies to improve adherence– Schedule of medication-taking– Simplified, more convenient medication regimens (reduced dosing, injectable)– Organizing pills (pill boxes, reminder systems)– Regularly scheduled visits with a provider, even when the patient feels well– Individualize regimen to reduce adverse events and side effects

Dosing Frequency, Persistence, and Adherence in Transplant Recipients Dosing Frequency, Persistence, and Adherence in Transplant Recipients

• 219 patients (45% male; 3±2 years post transplantation) randomized to tacrolimus 145 once daily or 74 twice daily

• Persistence at 6 months: 81.5% of the once-daily group vs 71.9% of the twice-daily group remained with the treatment (P=0.0824)

• Adherence: 88.2% of the once-daily group and 78.8% of the twice-daily group (P=0.0009)

• Doses were missed more frequently in the evening than in in the morning (11.7% vs 14.2%; P=0.0035; twice daily regimen)

Kuypers DR et al. Transplantation. 2013;95;333-340.

Case Report Management Case Report Management

• Patient was treated with steroid pulse, 3 doses of IVIG 70 g, and rituximab 1,000 mg X 2 over 2 weeks

• Liver function tests remained normal

ConclusionsConclusions

• Candidates for SLK transplant include:– ESRD

– Metabolic kidney diseases cured by liver transplant

– Other?

• AMR is a common cause of death-censored transplant failure

• Currently, management of AMR must include maintenance of immunosuppression while optimizing patient adherence and minimizing side effects

– Recognize those at risk for low–adherence

• Future therapies will address underlying pathophysiology of AMR

Participant CME EvaluationParticipant CME Evaluation

• Please take out the Participant CME Post-activity Survey and Evaluation from the back of your packet

• If you are not seeking credit, we ask that you still fill out the information pertaining to your degree and specialty, as well as the few questions we will read through now measuring the knowledge and competence you have garnered from this program.

Post-activity Survey Question 1Post-activity Survey Question 1

After attending this activity, how confident are you in your ability to select a candidate for simultaneous liver-kidney transplantation (SLK):

1 2 3 4 5



After attending this activity, how confident are you in recognizing the signs and symptoms of antibody-mediated rejection (AMR):

1 2 3 4 5



Liver transplant candidates with stage 4-5 chronic kidney disease (CKD) should be receiving an SLK?

A. CorrectB. IncorrectC. I don’t know


A 60-year-old male with a history of type 2 diabetes mellitus (5-yr) and liver disease secondary to NASH is evaluated for liver transplantation. He has never been told he had kidney disease. Labs: Serum creatinine: 3.2 mg/dL (up from 1.2 mg/dL a year earlier, and 1.5 mg/dL 4 days ago); Urine output: 690 mL per day (down from 1.2 liters 4 days ago); Serum Na+ 129 mEq/L; Serum K+ 5.8 mEq/L; Urine: PCR 0.3 mg/g; Na+ 12 mEq/L.

Is this patient a dual liver/kidney transplant candidate?A. YesB. NoC. I don’t know


In liver transplant recipients with eGFR >30 mL/min/1.73 m2, compared to standard tacrolimus dosing, the addition of everolimus to reduced tacrolimus did which of the following:

A. Prevented kidney function loss but increased the incidence of acute rejection, graft loss, and death

B. Prevented kidney function loss with similar impact on the incidence of acute rejection, graft loss, and death

C. Similarly reduced kidney function and the incidence of acute rejection, graft loss, and death

D. I don’t know


The most common cause of AMR is?

A. Viral infection

B. Non-adherence to regimen

C. Age of recipient

Thank you for joining us today!Thank you for joining us today!

Please remember to turn in your Please remember to turn in your evaluation form evaluation form to earn CME credit.to earn CME credit.

Your participation will help shape future Your participation will help shape future CME activities.CME activities.

Backup Slides For Speaker’s consideration

Documents

Prior to the start of the program, ensure you have the following printed program materials: