Should We Continue to Prioritize SLK Over KTA Recipients Sumeet - - PowerPoint PPT Presentation

Should We Continue to Prioritize SLK Over KTA Recipients

Sumeet Asrani MD MSc Baylor University Medical Center Dallas, Texas March 2020

Should We Continue to Prioritize SLK Over KTA Recipients

• Balancing equity and utility
• SLKT in current era
• Recommendations

Outline

Balancing equity and utility

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Competing interests

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SLKT

Given survival advantage of SLKT vs LTA

KTA

Given survival advantage to avoid remaining on the WL/dialysis

UTILITY greatest likelihood of medical benefit

• Too restrictive may not help sickest

patient.

• SLKT gain is < collective benefit for

giving kidney to two recipients.

• SLKT benefit if sick patient but not

maximized if need not critical. EQUITY impact those that are sickest

• Liberal policy minimizes benefit if futile

transplants.

• Denied KTA equitable access if SLKT at

high rate especially if death not imminent.

• SLKT sicker but deny first come first

served principle applied to KTA.

Balancing utility versus equity

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Ethical Implications of Multi-Organ Transplants OPTN Ethics committee 2019

• local candidates who meet eligibility

criteria

• and regional candidates who meet

eligibility and have a MELD score of at least 35 or status 1A.

• Within 150 nautical miles of the donor

hospital and have a MELD ≥ 15

• Within 250 nautical miles of the donor

hospital and have a MELD ≥ 29

• Within 250 nautical miles of the donor

hospital and status 1A or 1B.

Before allocating the kidney to KTA, host OPO must offer the kidney with the liver to

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Atleast true on Feb 25 2020 @10pm

1: Rising SLKT

247 280 340 401 445 379 362 388 413 462 494 558 627 730 739 677 728 100 200 300 400 500 600 700 800 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019

Number of SLKT

UNOS

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1: Rising SLKT

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0.09 0.01 0.02 0.03 0.04 0.05 0.06 0.07 0.08 0.09 0.1 Percent of LTA

Percent of LTA

0.03 0.005 0.01 0.015 0.02 0.025 0.03 0.035 0.04 0.045 Percent of KTA

Percent of KTA

9% of LTA 3% of KTA

Accessed Feb 19, 2020

UNOS

2: Center and regional variation in SLKT

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Percent SLKT

Nadim M et al AJT 2012

• RACE for multi organ transplantation:
• African Americans 18% multi organ transplantation vs. 35% single organ transplant
• INCOME for multi organ transplantation :
• Zip codes with higher median income (diff 5,717) for MOT
• CHARACTERISTICS for multi organ transplantation :
• Recipient age: 3.6 years older
• higher median and mean eGFR
• WL deaths higher
• KDPI 12% lower
• SLKT pull from one region and disadvantage KTA in that area?

3: SLKT vs. KTA systematically different

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4: Native renal recovery with SLKT

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Levitsky J et al AJT 2012

eGFR>20 eGFR>30 eGFR>40 51% 27% 17%

Among 77 patients that underwent renal scan out of 155 SLKT single center

• Constant discussion about utility and equity
• Rising SLKT
• Center and regional variation
• Higher quality organs → SLKT along with creation of disparities
• Renal recovery in a significant portion (?)

Summary of selected concerns

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SLKT in the current era: Is the need evolving?

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• 1. LT candidate in current era is inherently sicker

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2008 2018

ICU 11.5% 15% Age >65 yrs 11% 23% DM 25% 29% “NAFLD” 26% 33% MELD>35 12% 22% MELD 30-34 10% 21% Obese, BMI>30 34% 37%

Kwong A et al AJT 2020

• 1. There is more CKD pre LT: 8%→15%

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Cullaro J et al LT 2019

• 2. There is real CKD post LT

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Mazumder N et al ATC 2020 Measured GFR 1985-2015, 1100 recipients, 4700 measurements

1y 3y 5y GFR<60 CKD 24.1% 57.3% 61.2% ESRD 5.1% 5.8% 6%

• 3. SLKT: survival advantage in those with renal failure

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2002-2012, unadjusted analysis

• 3. SLKT: improved survival long term

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Paired Kidneys: Although kidneys allocated to SLK vs KT demonstrate worse short-term survival, this risk appears to be reversed when follow-up is extended long-term Cannon RM et al JACS 2019

Graft failure lower 11% vs 21% Graft survival longer 11 vs 10.5 years

• 4. SLKT criteria are now standardized

Candidates must meet at least one of the following conditions and confirm by Tx nephrologist:

1.CKD with GFR <60 mL/min for >90 days with:

• ESRD on chronic RRT, or
• GFR <30 at time of listing for kidney

2.Sustained AKI with:

• 6 consecutive weeks of RRT, or
• GFR <25 mL/min for 6 consecutive weeks, or
• Combination of 2a and 2b for 6 consecutive weeks

3.Metabolic disease (hyperoxaluria, aHUS, familial non-neuropathic systemic amyloidosis, or methylmalonic aciduria “Safety Net” Provision: Liver transplant recipients with continued dialysis dependency or GFR ≤ 20 ml/min in the period 2-12 months after liver transplant will receive priority for kidney allocation for kidneys with KDPI>20%

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• 4. Underlying principles of the new policy

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New Policy ↓ SLKT ↑KTA ↓”waste” Should be candidate but criteria Safety Net

• 4. Most SLKT meet CKD criteria

93.1 6.5 0.7 10 20 30 40 50 60 70 80 90 100 CKD AKI Metabolic

Criteria

~85% had severe renal dysfunction at time of transplant (>50% on dialysis)

51.8 22.7 9.7 15.8 10 20 30 40 50 60 DIALYSIS eGFR<20 eGFR 20-25 eGFR 25-30

CKD

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4: KALT Kidney graft survival

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SLKT N=6,774 KALT 2-12mo N=117 Mean KDPI (SD) 38 (26) 50 (22) DCD 4% 20% 1y 95% 94% 3y 93% 94% 5y 90% 81% 10y 83% 49% Obese, BMI>30 34% 37%

Jay CL et al JACS 2020 93 85 77

• 4. KALT Kidney graft survival (Safety net)

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Patient survival after liver transplant for SLKT and KALT (deceased donors only).

Overall kidney graft survival for SLKT and deceased donor KALT. Jay CL et al JACS 2020

• Registrants are sicker and may need SLKT more than before
• SLKT offers a survival advantage especially for patients on

dialysis

• There is acceptable long term graft survival
• New policy attempts to adjudicate candidates for SLKT and
• ffers a safety net with acceptable outcomes

Summary of recent changes

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Recommendations

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• Will a ↓ SLKT→ ↑ KALT
• SLKT criteria
• What happens to patients that do not quite meet SLKT criteria
• KALT
• Is KALT candidate different now compared to previous eras
• How many were too sick for safety net and never made it
• How many listed for safety net just in case but never received KALT
• Which patients won’t do well with safety net

− Age >60 years ad HD >90 d pre-LT

• 1. Scrutinize new policy: SLKT and safety net

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Pita A et al Trans Dir 2019

• 2. Standardize eGFR

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Unpublished data

All GFR GFR<60

Cirrhosis pts as compared to mGFR

WL 1-30 LT Day 31-90 LT Day 1 Yr LT Day 91- Yrs LT >1 -5 Yrs LT >5 -25

• 10

10 30 50

GRAIL MDRD6 MDRD4 CKD-EPI Method

Bias: Median difference (eGFR-mGFR)

• New eGFR developed in patients with

cirrhosis

• 13,021 GFR iothalamate samples (3,177

patients, 30 years) at Baylor

• GRAIL: Variables similar to MDRD-6

variables which included Age, Gender, Race, Scr, BUN, Alb

• GRAIL is more precise (95% CI) and

has less bias (eGFR-mGFR) as compared to other eGFR equations at low GFR (<30ml/min1.73m2)

Hepatology 2018

GRAIL correctly classified more patients with low GFR at baseline and KALT within 5 years after LT

Asrani S et al., Hepatology 2018

GRAIL

10 20 30 40 50 60 70 80 90 100 WL M1 M1-M3 Percent correct classification for mGFR<30ml/min/ 1.73m2

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Asrani SK et al Hepatology 2019

• 3. Biomarkers to predict renal recovery

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Levitsky, Baker et al. Hepatology 2014; Levitsky, Asrani et al Hepatology 2019 Northwestern discovery Baylor Cohort Validation

REVERSE Model: age, DM, OPN, TIMP-1 levels

• Better center-based risk stratification
• Can we predict need for 2nd organ better
• Systematic data collection, analysis and reporting
• A high-risk LTA liver may be upgraded to SLKT to improve
• utcomes as not counted in center reportable data
• 4. Monitoring of outcomes

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• Balancing utility and equity is difficult in SLKT
• SLKT is not (always) a waste of a kidney
• Approach needs to be streamlined
• Earlier LT and SLKT not needed?
• Scrutinize safety net
• Prioritization may need to be nuanced

Conclusion

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Should We Continue to Prioritize SLK Over KTA Recipients

Sumeet Asrani MD MSc Baylor University Medical Center Dallas, Texas March 2020