Are two better than one?

Are two better than one? Disclosures Ryutaro Hirose, MD Professor in Clinical Surgery University of California, San Francisco I have no relevant disclosures related to this presentation The PROBLEM There are 95,116 patients in the US waiting for a kidney transplant (9/20/2018) We performed 19,489 kidney transplants in the US in 2017 (15k DD) 35,000 30,000 25,000 20,000 15,000 10,000 US Organ Transplants 5,980 6,184 5,989 6,610 6,561 6,022 5,866 5,988 5,819 24% Increase 27,630 28,588 21,850 22,101 22,518 22,187 22,967 23,720 24,985 5,000 0 2009 2010 2011 2012 2013 2014 2015 2016 2017 deceased donor living donor Source: https://optn.transplant.hrsa.gov/data/view data reports/national data/ slide from Kevin O Connor CEOT 2018 1

US Deceased Donor Organs Recovered and Discarded 4864 4898 4439 4045 3966 4112 BUT the discard rate of kidney is quite high DISCARD RATE (2015 2016) was 19.7% DISCARD RATE Has been CLIMBING We haven t been able to decrease discards! 2012 2013 2014 2015 2016 2017 Source: OPTN DSA Dashboard for 2017 slide from Kevin O Connor CEOT 2018 and his personal correspondence with J. Rosendale Dilemma Two is definitely better than none (from the donor supply standpoint) PROBLEMS Wait time for transplant varies across the country Older individuals are not likely to get a Low KDPI kidney Mortality on dialysis is high Some useable kidneys are being discarded The Options Change organ allocation Not list as many patients (another controversy) Promote more organ donation All the potential will be in older donrs Use more of the less than perfect kidneys in an appropriate patient population incentivize this! High KDPI kidneys that are hard to place With high likelihood that they will not be used or transplanted Saving kidneys from the trash can 2

Two is better than none (from a candidate standpoint?) Definitely better than staying on dialysis Likely yes for those individuals that have to wait longer to get a better kidney offer KDRI DONOR FACTORS Age Height Weight Ethnicity (African American) Hypertension Diabetes Serum Creatinine HCV + DCD KDPI and age KDPI and graft survival 3

MORE BAD NEWS (unfortunately, not FAKE NEWS) NEWS FLASH WE ARE GETTING OLDER!! WE ARE GETTING FATTER!! Kidney Donor Trends Source: Stewart, D. E., Garcia, V. C., Rosendale, J. D., Klassen, D. K., & Carrico, B. J. (2017). Diagnosing the Decades-Long Rise in the Deceased Donor Kidney Discard Rate in the US. Transplantation. The Rising Deceased Donor Kidney Discard Rate in the U.S. Long-run increasing trend in median age, BMI, and KDRI among recovered kidney donors. 15 FIGURE 1. Trends in deceased donor kidneys recovered for transplant and the kidney discard rate, 1987 to 2015. The percentage of kidneys recovered for transplant but discarded rose from 5.1% in 1988, the first full year available, to 19.2% in 2009 and remained around 18% to 19% through 2015. The number of kidneys recovered for transplantation has more than doubled. Historical events potentially related to kidney recovery and discard, such as policy, system, or oversight changes, are annotated for reference. Stewart, Darren; Garcia, Victoria; Rosendale, John; Klassen, David; Carrico, Bob Diagnosing the Decades Long Rise in the Deceased Donor Kidney Discard Rate in the United States. Transplantation 2017; 101(3):575 587 3159 kidneys were discarded in 2015 4

Explaining the Kidney Discard Rate Trend (1999-2009) OPTN/SRTR 2016 Annual Data Report: Kidney Rates of kidneys recovered for transplant and not transplanted by KDPI Source: Stewart, D. E., Garcia, V. C., Rosendale, J. D., Klassen, D. K., & Carrico, B. J. (2017). Diagnosing the Decades-Long Rise in the Deceased Donor Kidney Discard Rate in the US. Transplantation. 5.7% rise 17 American Journal of Transplantation pages 18 113, 2 JAN 2018 DOI: 10.1111/ajt.14557 http://onlinelibrary.wiley.com/doi/10.1111/ajt.14557/full#ajt14557 fig 0035 Kidney Discard Rate: Pre (~5 years) vs. Post KAS (16 months) (p<0.0001) Why use two suboptimal kidneys? (p=0.55) (p=0.08) The use of ECD/high KDPI kidneys are associated with higher risk of graft failure Currently 20% of kidneys that are procured are DISCARDED and 59% of kidneys with KDPI >85% are DISCARDED After age 40, GFR, kidney mass begin to decrease with time, and reach 60% of baseline by 80 years of age Histology of renal senescence Intimal arterial thickening Arteriolar hyalinosis Interstitial Fibrosis/Tubular Atrophy Glomerular sclerosis Statistically significant rise for higher KDPI kidneys. 5

What is the Controversy About Dual Transplants? PRO Potential shorter wait time to transplant for appropriate recipients With appropriate selection of organs, outcomes are acceptable CON Kidney quality not the same as SCD I don t want the patient to get a bad kidney Inconsistent allocation criteria of dual organs UNOS Policy In areas where the wait time is long, death is more likely while waiting for a kidney on dialysis Concern about and adverse effect on SRTR data Longer and more complicated surgery Using up two kidneys for one recipient How to use high KDPI kidneys Reduction of cold ischemic time can improve graft outcome Reduction of CNI exposure Belatacept CNI sparing protocols in patients receiving ECD kidneys had better long term renal function DUAL KIDNEY TRANSPLANTS to increase nephron mass Outcomes of Dual Kidney transplant difficult to tease out Data is generally single center experience N is small Heterogeneity of donors (dual vs single), BUT Dual kidney recipients of donors with highest KDPI (e.g. >90) had a significantly higher 3 year graft survival rate 6

How to make decision single vs dual kidney? Biopsy? Has never been shown to correlate with any outcome Histologic scores egfr? Some use egfr <65 cc/min to allocate as duals KDPI? Dual Kidney Outcomes OPTN data Deceased donors > 50 yrs 2000 2005 Practical decision? OPO inability to place as single kidney Gill, J. Transplantation 2008;86 Which recipients should be considered to receive a dual kidney transplant? Age: Generally > age 50 yrs Consider a younger age for diabetics Size matters Consider nephron dose Weight or BMI match Anticipated wait time for transplant Consider the cardiovascular health of the recipient Those not well suited for dual kidneys Obese Prior pelvic surgery Higher cardiovascular risk Unable to tolerate induction with lymphocyte depleting agents UCSF recent experience dual kidney txp age Tx date Donor 6 mo Cr 1 yr Cr 2 yr Cr Last Cr Notes 1 60 7/28/13 ECD 0.91 Expired 2 yrs post 2 64 1/1/15 Type 1 DM 2.09 2.2 2.2 DKA 3 59 8/17/17 HCV + KDPI 53% 0.7 0.7 4 69 9/26/17 0.76 Reexp bleeding 5 65 9/30/17 KDPI 56%, 1.2 1.3 1.3 CMV DCD 6 68 10/5/17 KDPI 93% 0.89 0.89 Ureteral revision 7 67 10/7/17 KDPI 99% 1.06 1.06 8 59 4/2/18 KDPI 90% 1.17 1.17 PGS 9 65 5/29/18 KDPI 97% 0.98 CF 10 73 7/29/18 KDPI 98% 0.89 7

Death Censored Graft Survival UNOS Data 2002 2012 Tanriiover AJT 2014 Feb 1492) 404 415 Massie, Transplantation 2014;14 Complications with Dual Transplant What are the barriers? Concerns that the recipient could get a better kidney Concerns about SRTR data being underperforming center Lack of ability to have timely biopsy for review Prolonged cold ischemia times Remuzzi NEJM 2006 8

Regulatory Consideration Tension Between Transplant Center and OPO Performance Metrics Transplant Outcomes Better Patient and Graft survival at 1 and 3 years Organ Utilization Higher Conversion rates Organ Placement Slide Worse adapted from Kevin O Conner, Lower CEOT 2018 Massie. Transplantation 2014 Summary Questions? There are patients who would benefit from Dual Kidney Transplant There are kidneys we could be using as dual kidney transplant that we are currently discarding Need a way to allocate these kidneys to patients who will benefit the most How to abrogate the concern about impact on outcomes actually outcomes have been excellent! 9