In conclusion, HMP resulted in remarkably lower rates of DGF in renal grafts that were transplanted after a short CIT. Also, CIT remained an independent risk factor for DGF in HMP-preserved kidneys.

Background: Ischemia-reperfusion injury of donor kidneys may worsen transplant outcome. Kidneys with severe injury, such as kidneys of donors after circulatory death, develop edema, which may lead to renal compartment syndrome with reduced tissue perfusion. Objective: We studied the effect of capsulotomy during hypothermic machine perfusion (HMP) of ischemically damaged porcine kidneys. Methods: Eight pairs of kidneys from slaughterhouse pigs were assigned to two groups (20 and 45 min of warm ischemia). After 21 h of HMP, capsulotomy was performed, and perfusion was continued for 2 h. During perfusion, machine flow (Q), renal resistance (RR), renovascular circulating volume (RCV), intraparenchymal pressure (IPP) and weight were recorded. Parenchymal injury was examined with methylene blue infusion. Results: Mean Q and RCV increased directly after capsulotomy [percentage increase (95% confidence interval): ΔQ = 32% (17, 47), p = 0.001, and ΔRCV = 19% (3, 35), p = 0.023]. Mean RR decreased [ΔRR = -23% (-31, -15), p < 0.001]. Subanalysis comparing both warm ischemia groups showed no significantly different effect of capsulotomy between groups. There was no methylene blue leakage after capsulotomy in any kidney. Conclusions: Renovascular perfusion can be improved with capsulotomy during HMP, without damaging the renal parenchyma. Follow-up studies need to determine which donor kidneys may benefit from capsulotomy.

Extracellular histones are cytotoxic molecules involved in experimental acute kidney injury. In patients receiving a renal transplant from donors after circulatory death, who suffer from additional warm ischemia, worse graft outcome is associated with higher machine perfusate extracellular histone H3 concentrations. We now investigated temperature-dependent extracellular histone release in an ex vivo porcine renal perfusion model, and subsequently studied histone release in the absence and presence of non-anticoagulant heparin. Seven pairs of ischemically damaged porcine kidneys were machine perfused at 4°C (cold ischemia) or 28°C (warm ischemia). Perfusate histone H3 concentration was higher after warm as compared to cold ischemia (median (IQR) = 0.48 (0.20–0.83) μg/mL vs. 0.02 (0.00–0.06) μg/mL; p = .045, respectively). Employing immune-electron microscopy (EM), histone containing cytoplasmic protrusions of tubular and endothelial cells were found after warm ischemic injury. Furthermore, abundant histone localization was detected in debris surrounding severely damaged glomerular cells, in a “buck shot” pattern. In vitro, histones were cytotoxic to endothelial and kidney epithelial cells in a temperature-dependent manner. In a separate ex vivo experiment, addition of heparin did not change the total histone H3 levels observed in the perfusate but revealed a continuous increase in the level of a lower molecular weight histone H3 variant. Our findings show that ischemically damaged kidneys release more extracellular histones in warm ischemia, which by EM was due to histone release by renal cells. Blocking of histone-mediated damage during transplantation may be beneficial in prevention of renal injury.

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