Decrease of renal resistance during hypothermic oxygenated machine perfusion is associated with early allograft function in extended criteria donation kidney transplantation

Abstract

Hypothermic oxygenated machine perfusion (HOPE) was recently tested in preclinical trials in kidney transplantation (KT). Here we investigate the effects of HOPE on extended-criteria-donation (ECD) kidney allografts (KA). Fifteen ECD-KA were submitted to 152 ± 92 min of end-ischemic HOPE and were compared to a matched group undergoing conventional-cold-storage (CCS) KT (n = 30). Primary (delayed graft function-DGF) and secondary (e.g. postoperative complications, perfusion parameters) endpoints were analyzed within 6-months follow-up. There was no difference in the development of DGF between the HOPE and CCS groups (53% vs. 33%, respectively; p = 0.197). Serum urea was lower following HOPE compared to CCS (p = 0.003), whereas the CCS group displayed lower serum creatinine and higher eGFR rates on postoperative days (POD) 7 and 14. The relative decrease of renal vascular resistance (RR) following HOPE showed a significant inverse association with serum creatinine on POD1 (r = - 0.682; p = 0.006) as well as with serum urea and eGFR. Besides, the relative RR decrease was more prominent in KA with primary function when compared to KA with DGF (p = 0.013). Here we provide clinical evidence on HOPE in ECD-KT after brain death donation. Relative RR may be a useful predictive marker for KA function. Further validation in randomized controlled trials is warranted.Trial registration: clinicaltrials.gov (NCT03378817, Date of first registration: 20/12/2017).

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1

(A) Enrollment of hypothermic oxygenated machine perfusion (HOPE) preserved allografts, compared to a historical cohort transplanted after conventional cold storage (CCS) at the University Hospital RWTH Aachen, Aachen, Germany. (B) Connecting the renal artery to the renal artery cannula following back-table preparation. (C) Positioning of the allograft in the kidney holder mesh of the device. (D) The kidney holder mesh is closed. After its placement into the organ container the allograft is ready to be perfused. (E) Hypothermic oxygenated machine perfusion of the kidney allograft with the Kidney Transport Assist (Organ Assist b.v., Groningen, The Netherlands). ECD, Extended criteria donor; DBD, Donation after brain death, KT, kidney transplantation.

Figure 2

(A) Time course of serum creatinine levels during the early postoperative phase in the hypothermic oxygenated machine perfusion (HOPE) and conventional cold storage (CCS) groups (n = 45). Serum creatinine was higher after HOPE at postoperative day (POD) 7 (4.9 ± 2.2 mg/dl vs. 3.7 ± 3.2/ mg/dl p = 0.033) and POD 14 (4.1 ± 2.5 mg/dl vs. 2.6 ± 2.1 mg/dl p = 0.034). (B) Serum urea levels on POD1 were higher in CCS than in the HOPE group (78 ± 32 mg/dl vs. 103 ± 26 mg/dl p = 0.003; MWU). (C) Time course of serum creatinine levels in allografts with PF during the early postoperative days in HOPE and CCS groups (n = 24; MWU). Allografts with DGF were excluded, considering the effect of dialysis on these values. (D) Duration of hospital stay following kidney transplantation in HOPE and CCS groups (25 ± 13d vs. 21 ± 22d p = 0.570; MWU). (E) Postoperative 90-day complications assessed by the Clavien-Dindo (CD) classification following HOPE and CCS, without significant between-group differences. (F) Postoperative 90-day complications assessed by comprehensive complication index in HOPE and CCS groups (32 ± 22 vs. 36 ± 24 p = 0.647; MWU). *p < 0.05, **p < 0.01.

Figure 3

(A) Decrease of renal resistance (RR) during hypothermic oxygenated machine perfusion (HOPE). During the first hour of HOPE, RR changes significantly and reaches a plateau in the later phase of perfusion (Wilcoxon rank sum test). (B) Alterations of relative RR correlate with recipients’ serum creatinine on POD1 (Spearman's rank-order). (C) Development of flow and RR in kidney allografts with primary function (PF, blue) and delayed graft function (DGF, red) during HOPE. Initial flow was lower in the PF group (36 ± 22 ml/min vs. 77 ± 45 ml/min p = 0.040; MWU). (D) Increase of mean flow and decrease of mean RR compared to baseline during HOPE in PF and DGF kidney allografts. Mean alterations of flow and RR were higher in the PF than in the DGF group (RR: 54 ± 16% vs. 25 ± 15% p = 0.013; MWU) *p < 0.05, **p < 0.01 ***p < 0.001.