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

Outline • Balancing equity and utility • SLKT in current era • Recommendations Should We Continue to Prioritize SLK Over KTA Recipients

Balancing equity and utility 3

Competing interests KTA SLKT Given survival Given survival advantage to avoid advantage of remaining on the SLKT vs LTA WL/dialysis 4

Balancing utility versus equity EQUITY UTILITY impact those that are sickest greatest likelihood of medical benefit • Liberal policy minimizes benefit if futile • Too restrictive may not help sickest transplants. patient. • Denied KTA equitable access if SLKT at • SLKT gain is < collective benefit for high rate especially if death not imminent. giving kidney to two recipients. • SLKT sicker but deny first come first • SLKT benefit if sick patient but not served principle applied to KTA. maximized if need not critical. 5 Ethical Implications of Multi-Organ Transplants OPTN Ethics committee 2019

Before allocating the kidney to KTA, host OPO must offer the kidney with the liver to • • local candidates who meet eligibility Within 150 nautical miles of the donor hospital and have a MELD ≥ 15 criteria • • and regional candidates who meet Within 250 nautical miles of the donor hospital and have a MELD ≥ 29 eligibility and have a MELD score of at least 35 or status 1A. • Within 250 nautical miles of the donor hospital and status 1A or 1B. 6 Atleast true on Feb 25 2020 @10pm

1: Rising SLKT 800 739 730 728 700 677 627 600 558 Number of SLKT 494 500 462 445 413 401 388 400 379 362 340 280 300 247 200 100 0 7 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 UNOS

1: Rising SLKT Percent of LTA Percent of KTA 0.1 0.045 0.09 0.09 0.04 0.08 0.035 0.03 0.07 Percent of KTA 0.03 Percent of LTA 0.06 0.025 0.05 0.02 0.04 0.015 0.03 0.01 0.02 0.005 0.01 0 0 9% of LTA 3% of KTA 8 Accessed Feb 19, 2020 UNOS

2: Center and regional variation in SLKT Percent SLKT 9 Nadim M et al AJT 2012

3: SLKT vs. KTA systematically different • 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? 10

4: Native renal recovery with SLKT eGFR>20 eGFR>30 eGFR>40 51% 27% 17% 11 Among 77 patients that underwent renal scan out of 155 SLKT single center Levitsky J et al AJT 2012

Summary of selected concerns • 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 (?) 12

SLKT in the current era: Is the need evolving? 13

1. LT candidate in current era is inherently sicker 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% 14 Kwong A et al AJT 2020

1. There is more CKD pre LT: 8% → 15% 15 Cullaro J et al LT 2019

2. There is real CKD post LT 1y 3y 5y GFR<60 CKD 24.1% 57.3% 61.2% ESRD 5.1% 5.8% 6% 16 Measured GFR 1985-2015, 1100 recipients, 4700 measurements Mazumder N et al ATC 2020

3. SLKT: survival advantage in those with renal failure 17 2002-2012, unadjusted analysis

3. SLKT: improved survival long term Graft survival longer 11 vs 10.5 years Graft failure lower 11% vs 21% Paired Kidneys: Although kidneys allocated to SLK vs KT demonstrate worse short-term survival, this risk 18 appears to be reversed when follow-up is extended long-term Cannon RM et al JACS 2019

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% 19

4. Underlying principles of the new policy ↑KTA ↓ SLKT ↓”waste” New Policy Should be candidate but Safety Net criteria 20

4. Most SLKT meet CKD criteria Criteria CKD 100 60 93.1 51.8 90 50 80 70 40 60 50 30 22.7 40 20 15.8 30 9.7 20 10 6.5 10 0.7 0 0 CKD AKI Metabolic DIALYSIS eGFR<20 eGFR 20-25 eGFR 25-30 ~85% had severe renal dysfunction at time of transplant (>50% on dialysis) 21

77 93 85 4: KALT Kidney graft survival SLKT KALT 2-12mo N=6,774 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% 22 Jay CL et al JACS 2020

4. KALT Kidney graft survival (Safety net) Patient survival after liver transplant for SLKT and Overall kidney graft survival for SLKT KALT (deceased donors only). and deceased donor KALT. 23 Jay CL et al JACS 2020

Summary of recent changes • 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 offers a safety net with acceptable outcomes 24

Recommendations 25

1. Scrutinize new policy: SLKT and safety net • 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 26 Pita A et al Trans Dir 2019

2. Standardize eGFR GFR<60 All GFR 27 Cirrhosis pts as compared to mGFR Unpublished data

• New eGFR developed in patients with 50 cirrhosis Bias: Median difference (eGFR-mGFR) 30 • 13,021 GFR iothalamate samples (3,177 patients, 30 years) at Baylor 10 • GRAIL: Variables similar to MDRD-6 variables which included Age, Gender, -10 Race, Scr, BUN, Alb WL LT Day LT Day LT Day 91- LT >1 -5 LT >5 -25 1-30 31-90 1 Yr Yrs Yrs • GRAIL is more precise (95% CI) and has less bias (eGFR-mGFR) as Method CKD-EPI MDRD4 MDRD6 GRAIL compared to other eGFR equations at low GFR (<30ml/min1.73m 2 ) Hepatology 2018

GRAIL 100 Percent correct classification for mGFR<30ml/min/ 90 80 70 60 1.73m2 50 40 30 20 10 0 WL M1 M1-M3 GRAIL correctly classified more patients with low GFR at baseline and KALT within 5 years after LT 29 Asrani SK et al Hepatology 2019 Asrani S et al., Hepatology 2018

3. Biomarkers to predict renal recovery Northwestern discovery Baylor Cohort Validation REVERSE Model: age, DM, OPN, TIMP-1 levels 30 Levitsky, Baker et al. Hepatology 2014; Levitsky, Asrani et al Hepatology 2019

4. Monitoring of outcomes • Better center-based risk stratification • Can we predict need for 2 nd organ better • Systematic data collection, analysis and reporting • A high-risk LTA liver may be upgraded to SLKT to improve outcomes as not counted in center reportable data 31

Conclusion • 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 32

Should We Continue to Prioritize SLK Over KTA Recipients Sumeet Asrani MD MSc Baylor University Medical Center Dallas, Texas March 2020