Ischemic postconditioning in human DCD kidney transplantation is feasible and appears safe

Abstract

SummaryIschemic postconditioning may improve outcome after kidney transplantation. We performed a pilot study to assess feasibility and safety of ischemic postconditioning in human donation-after-circulatory-death kidney transplantation. Twenty patients were included. Primary outcome was rate of serious adverse events. Secondary outcomes were incidence of DGF and renal function at 3 months. Data were compared to a historical control group (n = 40). Furthermore, we performed a paired kidney analysis using the contralateral kidney (n = 11). Donor age and serum creatinine were higher in the experimental group compared with historical control: 57.7 (20-71) vs. 51.5 (24-74) years (P = 0.01) and 79 (40-156) lmol/l vs. 64 (25-115) lmol/l (P = 0.047). Postconditioning could be applied all times. One complication, a venous tear, occurred related to postconditioning. The experimental group experienced more DGF (85% vs. 63%) (P = 0.07). Serum creatinine at month 3 was 166 (109-331) lmol/l vs. 159 (81-279) lmol/l (P = 0.71). Paired kidney analysis showed no significant differences in DGF (72.2% vs. 54.5%, P = 0.66) and serum creatinine 199 (90-473) lmol/l vs. 184 (117-368) lmol/l (P = 0.76). This is the first report of applying IPoC in human kidney transplantation. Although IPoC is feasible and appears to be safe, no benefit in terms of reduced DGF or better renal function was observed (Dutch trial registry number NTR 3117).

Aged kidneys are refractory to ischemic postconditioning in a rat model

“…19,20 A recent clinical report demonstrated that IPoC has no benefit in terms of reduced DGF or better renal function after kidney transplantation. 13 In this clinical report, donors were older and obviously had some kind of comorbidity. This was the first report of IPoC in human kidney transplantation.…”

“…In this clinical report donors were older and obviously had some kind of comorbidity. 13 It remained to be determined whether the lost protective effects of IPoC were associated with aging in vivo. The major purpose of this study was to determine whether kidneys from older rat were refractory to protection induced by IPoC.…”

“…[2][3][4][5][6][7][8][9][10][11][12] However, a recent disappointed clinical report demonstrated that IPoC has no benefit in terms of reduced delayed graft function (DGF) or better renal function after kidney transplantation, although IPoC is feasible and appears safe. 13 One explanation is that healthy young animals were used in most experimentation on animals. In this clinical report donors were older and obviously had some kind of comorbidity.…”

Increasing the Tolerance of DCD Hearts to Warm Ischemia by Pharmacological Postconditioning

“…Importantly in terms of clinical translation, our cardioprotective strategy was effective when administered postmortem. Postconditioning is a phenomenon that has been demonstrated in multiple other organs including kidney, liver and lungs (29)(30)(31)(32). Hence, our findings may also have implications for other organs retrieved from DCD donors.…”

Neutrophil Gelatinase-Associated Lipocalin, but Not Kidney Injury Marker 1, Correlates with Duration of Delayed Graft Function

“…The study was monitored by an independent Data Safety Monitoring Board. The clinical results of the ‘PINK' study have been published recently [17]. Within this clinical study, we collected perfusate and serum samples to search for biomarkers predictive of DGF and its recovery.…”