#1645 The role of donor Cystatin-C in posttransplant outcomes in kidney transplantation
Authors: Michelakis Ioannis , Fawaz Sarah , Vaughan Rebecca , Hartling Ivan , Charles Philip , Sharples Edward , Marinaki Smaragdi , Boletis Ioannis , Ploeg Rutger , Kaisar Maria 
Published: May 2024

Abstract

Background and Aims
Cystatin-C is an established marker of glomerular filtration rate in kidney disease. High levels of cystatin-C have been associated with unfavorable outcomes (acute kidney injury, cardiovascular morbidity) in critically ill patients. The aim of this study was to evaluate the levels of Cystatin-C in donors after brain (DBD) and circulatory death (DCD) and investigate its association with posttransplant graft function.

Method
Plasma samples from 303 donors (283 deceased, 20 living donors; LD) were obtained from the Quality in Organ Donation (QUOD) and the Oxford Transplant (OTB) biobanks. QUOD is a national multi-center UK wide bioresource of deceased donor clinical samples collected during donor management and organ procurement. OTB is a living donor biobank established to obtain clinical samples as control cohorts. Only deceased donors with both grafts transplanted were included in the study. Plasma Cystatin-C from LD samples as assessed as an optimal control group. The samples were linked to donor and recipient metadata obtained from the National Transplant Registry (NHSBT). Using Luminex assays, plasma Cystatin-C was quantified in samples collected during donor management (prior to cross clamp in DBDs and LDs and at withdrawal of support in DCDs). We performed descriptive statistics and multivariate linear and logistic analysis to determine the association between Cystatin-C, primary non-function (PNF), delayed graft function (DGF), acute rejection (AR) and 12-month posttransplant graft function.

Results
Among 303 donors (median age: 50 years), 126 were DCDs, 157 DBDs (20.1% of them were expanded criteria donors, ECD) and 20 LDs. ECDs and DCDs had significantly higher levels of Cystatin-C, compared to DBDs.
In a total of 606 recipients, 11 (1.9%) developed PNF, and 128 (21%) developed DGF (24 as pairs, 80 non-pairs). Forty-six recipients (7.6%) experienced at least one AR episode and 60 (10%) donors had lost the graft during follow-up. Donor levels of Cystatin-C were associated with DGF and were further elevated in donors of kidneys which developed PNF (P-value &lt; .0001, Fig. 1). Grafts with acute rejections were retrieved from donors with higher levels of Cystatin-C, but the difference did not meet statistical significance.
Cystatin-C levels were significantly lower (P-value &lt; .0001) in donors who offered concordant grafts with optimal 12-month post-transplant function (eGFR &gt;60 ml/min), compared with grafts with intermediate function (GFR 30-60 ml/min) or eGFR &lt;30ml/min (Fig. 2).
LDs had significantly lower levels of Cystatin-C compared to deceased donors in all studied outcomes (Figs 1 and 2).
Cystatin-C during donor management was an independent risk factor for inferior 12-month paired graft function, after the implementation of three different multivariate models, including donor (β-coef = −11.3, P-value = .001), recipient (β-coef = −16, P-value &lt; .001) and post-transplant characteristics (β-coef = −13.1, P-value = .002).

Conclusion
In a large cohort of deceased and living donors, we were able to evaluate the circulating levels of Cystatin-C during donor management with the use of high-end performance technology. The concentration of Cystatin-C was notably different among donor types and was significantly higher in donors with kidneys that developed PNF or had suboptimal graft function 12-month posttransplant. Our findings suggest that Cystatin-C may have a role in identifying higher-risk donors during donor management and offers the opportunity for granular assessment of donor kidney quality prior to transplantation.