DEFINING A NEW TOOL FOR LIMITING DELAYED GRAFT FUNCTION FOR KIDNEYS IN COLD STORAGE: THE

MACHINE PRESERVATION TO COLD ISCHEMIA TIME RATIO

Michael J. Goldstein1,2, Nikolina Icitovic1, and Yuriy Yushkov1 (1) New York Organ Donor Network, New York, NY

(2) Mount Sinai Medical Center, New York, NY

Background

• We have previously shown that MMRR at 3 hours is the most sensitive tool for predicting DGF and Graft Survival

<0.20.2-0.3

>0.3

0.70

0.80

0.90

1.00

0 100 200 300 400analysis time

Kaplan-Meier survival estimates: Resistance at 3 hours

p=0.0412

Hypothesis

• Increasing proportion of machine perfusion time (MPT) relative to total cold ischemia (CIT) for organs with variable periods of cold storage (CST) will reduce DGF and improve long term organ function.

Methods

• Analysis was performed on 1,088 deceased donor kidneys that were transplanted in a large Donor Service Area during years 2007-2009.

• The organs were analyzed in cohorts by the relative contribution of machine preservation time (MPT) and cold storage time (CST) to total cold ischemia time (CIT).

• Fisher’s Exact Test with ANOVA were used to compare the incidence of delayed graft function (DGF) and the impact of pump to total cold ischemia time ratio (PCR) by cohort. Univariate Cox Proportional Hazard Model was used to study the impact of MPT and CST on eGFR and allograft survival.

1,088 local and import kidneys

0

10

20

30

40

pump_hrs

0 10 20 30 40

ice_hrs

No DGF DGF

Ice Time vs Pump Time - ECD

0

10

20

30

40

pump_hrs

0 10 20 30 40

ice_hrs

No DGF DGF

Ice Time vs Pump Time - SCD

4 4 %

3 9 %

4 3 %

3 8 %3 6 %

2 9 %

3 1 %

2 7 %

3 7 %

3 0 %

3 3 %

3 0 %

3 3 %

- 1 0 %

0 %

1 0 %

2 0 %

3 0 %

4 0 %

5 0 %

6 0 %

7 0 %

0 - 4 h r s 5 - 8 h r s 9 - 1 2 h r s 1 3 - 1 6 h r s 1 7 - 2 0 h r s 2 1 - 2 4 h r s 2 5 - 2 8 h r s

% o f D G F b y P u m p T i m e

E C D S C D

E C D P - v a l u e = 0 . 6 3 3 , S C D P - v a l u e = 0 . 5 7 6

3 3 %

4 3 %4 4 %

4 1 %

3 7 %

3 7 %

4 7 %

5 8 %

2 9 %

2 8 %

1 2 %

2 9 %

3 1 %

4 7 %

4 0 %

5 2 %

4 2 %

0 %

1 0 %

2 0 %

3 0 %

4 0 %

5 0 %

6 0 %

7 0 %

0 - 4 h r s 5 - 8 h r s 9 - 1 2 h r s 1 3 - 1 6 h r s 1 7 - 2 0 h r s 2 1 - 2 4 h r s 2 5 - 2 8 h r s 2 9 - 3 2 h r s 3 3 - 3 6 h r s

% o f D G F v s . I c e T i m e

E C D S C D

E C D P - v a l u e = 0 . 5 8 2 , S C D P - v a l u e = 0 . 0 0 3

Predicted Probability of DGF

0

10

20

30

40

pump_hrs

0 10 20 30 40

ice_hrs

No DGF DGF

Ice Time vs Pump Time - SCD

Impact of MPT on DGF

0

10

20

10H

20H

30H

40H0

10

20

30

40

50

60

% DGF

Cold storage

delayed MPT

50-60

40-5030-40

20-3010-20

0-10

R-Square 0.7419

p = 0.0163

p=0.08

p=0.23

R-Square 0.6525P = 0.05

R-Square 0.9971P = 0.05

p=0.017

p=0.014

p=0.53

p=0.8731

p=0.9098

p=0.5336

p=0.0148

p=0.1978

p=0.0616*

3 Year Graft Survival by PCR QuartileMMRR <0.2

MMRR 0.2-0.3 MMRR >0.3

p=0.1535

p=0.715

p=0.7276

Conclusions

• Increasing PCR can reduce the impact of CIT on DGF

• Increasing PCR has more impact on DGF for organs with prolonged periods of CIT

• Organs with inferior quality (ECD, higher MMRR) are more sensitive to effects of increasing PCR

Conclusions

• There is an association between PCR and improved eGFR for organs with higher MMRR and prolonged CIT

• Early graft survival does NOT seem to be affected by changes in PCR with respect to MMRR cohorts