1. Kidney Transplantation.
Biomarkers Measured in Hypothermic Machine Preservation used as sensitive viability test prior
Kidney Transplantation.
E. Ablorsu, P. Laftsidis, B. Cook, L. Szabo
Cardiff Transplant Unit, UHW
Background
Methods - 1
Organ donor characteristics (presence of DM, hypertension, impaired function), length of warm ischaemia time (WIT) and cold ischaemia time (CIT) have detrimental impact on outcomes of kidney transplantation.
However, these donors remain important source to overcome persistent organ shortage. Therefore, there is increasing need to develop sensitive viability testing method prior transplantation to predict post-transplant graft function.
We analysed prospectively collected data of 130 DCD kidney transplants performed in a single centre from 1 January 2010 to 22 October Subsequently we compared DCD kidneys preserved on HMP (N=52), using the LifePort© (from Organ Recovery Systems) to DCD kidneys stored in Cold Storage (CS) (N=78). We excluded DCD kidneys transplanted in combination with pancreas and those performed as double transplants.
Between these two groups, we compared the incidence of functional delayed graft function (failure to decrease serum creatinine by at least 10% daily on 3 successive days during the first post-transplant week, fDGF), and glomerular filtration rate.
Outcomes - 1
Objectives
There is sufficient evidence, that Hypothermic Machine Presearvation (HMP) is excellent tool evaluate, improve quality of kidney graft and reduce preservation injury; even more in marginal donors.
There are suggestions, that some acute kidney injury bio-markers (NGAL, KIM-1, GST, mRNA) can be measured in perfusate of HMP and used to assess kidney tissue viability and predict graft function after transplantation. Level of these molecules correlates with extense of ischaemia (warm, cold) and level of acute kidney damage.
Functional DGF was lower in MP group compared to CS group but not significant (74.4% vs. 67.4%, p=0.27).
The glomerular filtration rate was similar at any time point.
Survival
Summary- 1
Donor age, CIT and type of storage correlated with fDGF
These results suggest that MP has a positive impact on early graft function on DCD kidneys and can neutralise the adverse effect of cold preservation, leading to at least equivalent early graft function and similar incidence of DGF compared to kidneys preserved by static CS. p
Exp(B)
Donor age
0.038
1.09
CIT
0.031
1.114
MP / CS
0.43
2.50
Constant
0.049
0.037
Methods - 2
Summary - 2
We are collecting perfusate sample from HMP, hourly first three hours; measure level of bio- markers and correlate to:
donor characteristics (age, co-morbidity, donor type, kidney function, cause of death)
transplant characteristics (warm and cold ischaemia),
HMP data (flow, resistance)
transplant outcomes (function, failure, survival).
Aim is to collect and analyse samples from 40 consecutive kidney transplants where kidney was HMP preserved.
Currently we are completing pilot study.
Preliminary data showed that these molecules, we identified as potential bio- markers of acute kidney injury and kidney tissue viability; are detectable at same concentration in perfusate as it can be measured in plasma and urine.
Prior making any final conclusion, we need to enrol more patients into the study.
We are convicted, that HMP perfusate is good medium to be used for measurement of biomarkers of kidney tissue injury and use it as viability test prior transplantation.
References:
1/ O’Callagham JM, Morgan RD, Knight SR, Morris PJ. Systemic review and meta-analysis of hypothermic machine pr=erfusion versus statis cold storage of kidney allografts on transplant outcomes. Br J Srg Jul;100(8):
2/ Bhangoo RS, Hall IE, Reese PP, Parikh CR; Deceased-donor kidney perfusion and urine biomarkers for kideny allograft outcomes: a systemic review. Nephrol Dial Transplant; Aug;27(8):